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Aalam AA, Krivitsky Aalam A, Yermian N, Choukroun J. Use of Advanced Platelet-Rich Fibrin for the Treatment of Multiple Adjacent Mucogingival Recessions: A Technical Report of the Fibrin-Assisted Soft-Tissue Promotion Protocol. J ESTHET RESTOR DENT 2025; 37:1184-1191. [PMID: 39425579 DOI: 10.1111/jerd.13341] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2024] [Revised: 09/16/2024] [Accepted: 10/02/2024] [Indexed: 10/21/2024]
Abstract
OBJECTIVES Platelet-rich fibrin (PRF) has had a marked impact on regenerative medicine due to its widespread ability to promote angiogenesis to defective tissues. Particularly in the dental field, evidence from randomized clinical trials has further shown that PRF facilitates greater soft-tissue regeneration when compared with hard tissues. CLINICAL CONSIDERATIONS Recently, the fibrin-assisted soft-tissue promotion (FASTP) technique has been developed as a means to promote soft-tissue regeneration of mucogingival recessions utilizing PRF. Within the present case report, a 28-year-old male presented with multiple adjacent mucogingival recessions in the maxilla ranging in probing depths (1-3 mm) and gingival recessions (1-5 mm). For optimal regenerative outcomes, the use of advanced PRF (A-PRF; 1300 RPM for 8 min) has been utilized to enhance regenerative outcomes by fully taking advantage of the low-speed centrifugation concept (LSCC). CONCLUSIONS This case report highlights the latest surgical concepts, centrifugation protocols, and use of the LSCC to regenerate multiple adjacent mucogingival recessions in the esthetic zone.
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Affiliation(s)
- Alexandre-Amir Aalam
- Clinical Associate Professor, Department of Advanced Periodontics, USC School of Dentistry, Los Angeles, California, USA
| | - Alina Krivitsky Aalam
- Clinical Associate Professor, Department of Advanced Periodontics, USC School of Dentistry, Los Angeles, California, USA
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Xue B, Han X, Zhu H, Li Q, Zhang Y, Bai M, Li Y, Li Y, Qin M, Nakajima T, Wang W, Gong JP, Cao Y. Hydrogels with prestressed tensegrity structures. Nat Commun 2025; 16:3637. [PMID: 40240377 PMCID: PMC12003825 DOI: 10.1038/s41467-025-58956-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2024] [Accepted: 04/07/2025] [Indexed: 04/18/2025] Open
Abstract
Tensegrity structures are isolated rigid compression components held in place by a continuous network of tensile components, and are central to natural systems such as the extracellular matrix and the cell cytoskeleton. These structures enable the nonreciprocal mechanical properties essential for dynamic biological functions. Here, we introduce a synthetic approach to engineer hydrogels with tensegrity architectures, drawing inspiration from the mechanochemical principles underlying biological systems. By employing in-situ enzyme-induced amino acid crystal growth within preformed polymeric networks, we achieve a hierarchical integration of micro crystal sticks randomly interlocked in the prestressed polymer matrice. This design mirrors natural tensegrity structures, balancing mechanical forces to maintain high stiffness (tensile moduli up to 30 MPa), fracture toughness (2600 J m⁻²), and water content (exceeding 80%). The resultant hydrogels exhibit bimodulus behavior due to their tensegrity structure, featuring a tensile-to-compressive modulus ratio of 13. This biomimetic approach provides a strategy for creating robust, adaptive materials for applications in tissue engineering and beyond.
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Affiliation(s)
- Bin Xue
- Collaborative Innovation Center of Advanced Microstructures, National Laboratory of Solid State Microstructure, Department of Physics, Nanjing University, Nanjing, China.
- Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou, China.
| | - Xu Han
- Collaborative Innovation Center of Advanced Microstructures, National Laboratory of Solid State Microstructure, Department of Physics, Nanjing University, Nanjing, China
| | - Haoqi Zhu
- Collaborative Innovation Center of Advanced Microstructures, National Laboratory of Solid State Microstructure, Department of Physics, Nanjing University, Nanjing, China
| | - Qingtai Li
- Collaborative Innovation Center of Advanced Microstructures, National Laboratory of Solid State Microstructure, Department of Physics, Nanjing University, Nanjing, China
| | - Yu Zhang
- Collaborative Innovation Center of Advanced Microstructures, National Laboratory of Solid State Microstructure, Department of Physics, Nanjing University, Nanjing, China
| | - Ming Bai
- Collaborative Innovation Center of Advanced Microstructures, National Laboratory of Solid State Microstructure, Department of Physics, Nanjing University, Nanjing, China
| | - Ying Li
- Institute of Advanced Materials and Flexible Electronics (IAMFE), School of Chemistry and Materials Science, Nanjing University of Information Science & Technology, Nanjing, China
| | - Yiran Li
- Collaborative Innovation Center of Advanced Microstructures, National Laboratory of Solid State Microstructure, Department of Physics, Nanjing University, Nanjing, China
| | - Meng Qin
- Collaborative Innovation Center of Advanced Microstructures, National Laboratory of Solid State Microstructure, Department of Physics, Nanjing University, Nanjing, China
| | - Tasuku Nakajima
- Institute for Chemical Reaction Design and Discovery (WPI-ICReDD), Hokkaido University, Sapporo, Japan
- Faculty of Advanced Life Science, Hokkaido University, Sapporo, Japan
| | - Wei Wang
- Collaborative Innovation Center of Advanced Microstructures, National Laboratory of Solid State Microstructure, Department of Physics, Nanjing University, Nanjing, China.
- Institute for Brain Sciences, Nanjing University, Nanjing, China.
| | - Jian Ping Gong
- Institute for Chemical Reaction Design and Discovery (WPI-ICReDD), Hokkaido University, Sapporo, Japan.
- Faculty of Advanced Life Science, Hokkaido University, Sapporo, Japan.
| | - Yi Cao
- Collaborative Innovation Center of Advanced Microstructures, National Laboratory of Solid State Microstructure, Department of Physics, Nanjing University, Nanjing, China.
- Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou, China.
- Institute for Brain Sciences, Nanjing University, Nanjing, China.
- Chemistry and Biomedicine innovation center, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, China.
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Liu H, Li M, Li S, Zhang C, Feng J. Simulation study on parameter dependence of dynamic osteocyte response under low-magnitude high-frequency vibration. Med Eng Phys 2025; 137:104307. [PMID: 40057366 DOI: 10.1016/j.medengphy.2025.104307] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2023] [Revised: 12/03/2024] [Accepted: 02/05/2025] [Indexed: 05/13/2025]
Abstract
The dynamic response mechanism of osteocytes to whole-body low-amplitude high-frequency vibration (LMHFV) is investigated using numerical simulation. In this study, a finite element model of a single bone lacuna-osteocyte incorporating the cytoskeleton was established. The vibration parameter dependence characteristics (acceleration amplitude (a), frequency (f)) of the dynamic osteocyte response under LMHFV were simulated. The results demonstrate that the alternating positive and negative liquid pressure acted on the osteocyte under LMHFV protocols (0.01 g-0.05 g, 30 Hz) (g=gravitational acceleration, 1 g = 9.8 m/s2) and the fluid shear stress increase with the acceleration amplitude. Additionally, the absolute values of positive and negative liquid pressure are relatively higher in the parameters range (0.026 g-0.038 g, 30 Hz). The von Mises stress extreme value of the microtubules presents a non-linear variation with increasing vibration parameters. Moreover, cytoskeletons can generate higher stress under vibration protocols (0.02 g-0.03 g, 30-45 Hz), thus facilitating the transmission of mechanical signals while satisfying the mechanical strength conditions compared to other reasonable vibration parameter range (0.01 g-0.05 g, 30-45 Hz). In summary, LMHFV with appropriate parameters can improve the mechanical microenvironment of osteocytes and enhance cell bioactivity to some extent.
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Affiliation(s)
- Haiying Liu
- Tianjin Key Laboratory for Advanced Mechatronic System Design and Intelligent Control, School of Mechanical Engineering, Tianjin University of Technology, Tianjin 300384, PR China; National Demonstration Center for Experimental Mechanical and Electrical Engineering Education, Tianjin University of Technology, Tianjin 300384, PR China
| | - Mingzhi Li
- Tianjin Key Laboratory for Advanced Mechatronic System Design and Intelligent Control, School of Mechanical Engineering, Tianjin University of Technology, Tianjin 300384, PR China; National Demonstration Center for Experimental Mechanical and Electrical Engineering Education, Tianjin University of Technology, Tianjin 300384, PR China
| | - Shenggang Li
- Tianjin Key Laboratory for Advanced Mechatronic System Design and Intelligent Control, School of Mechanical Engineering, Tianjin University of Technology, Tianjin 300384, PR China; National Demonstration Center for Experimental Mechanical and Electrical Engineering Education, Tianjin University of Technology, Tianjin 300384, PR China
| | - Chunqiu Zhang
- Tianjin Key Laboratory for Advanced Mechatronic System Design and Intelligent Control, School of Mechanical Engineering, Tianjin University of Technology, Tianjin 300384, PR China; National Demonstration Center for Experimental Mechanical and Electrical Engineering Education, Tianjin University of Technology, Tianjin 300384, PR China
| | - Jingjing Feng
- Tianjin Key Laboratory for Advanced Mechatronic System Design and Intelligent Control, School of Mechanical Engineering, Tianjin University of Technology, Tianjin 300384, PR China; National Demonstration Center for Experimental Mechanical and Electrical Engineering Education, Tianjin University of Technology, Tianjin 300384, PR China.
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Schlattmann B, Kiyono K, Kelty-Stephen DG, Mangalam M. Angular distribution of fractal temporal correlations supports adaptive responses to wobble board instability. J R Soc Interface 2025; 22:20240664. [PMID: 39904365 PMCID: PMC11793983 DOI: 10.1098/rsif.2024.0664] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2024] [Revised: 11/17/2024] [Accepted: 12/02/2024] [Indexed: 02/06/2025] Open
Abstract
Contemporary dynamical models of human postural control propose an intermittent controller regulating the postural centre of pressure (CoP) about a stable saddle-shaped manifold along anatomical anteroposterior (AP) and mediolateral (ML) axes, releasing CoP in an outwards spiral when inactive. Experimental manipulations can evoke this saddle-type topology in fractal temporal correlations along the AP axis and reducing correlations along the ML axis. However, true effects of task demands may often manifest within angular space between anatomical AP and ML axes-a space not typically modelled explicitly. We tested how instability and attentional load influence postural control across the full angular range of fractal variability along the two-dimensional (2D) support surface. Forty-eight healthy young adults performed a suprapostural Trail Making Test (TMT) while standing on a wobble board, inducing continuous perturbations along the ML axis. Stable, quiet standing exhibited classic saddle-like topology, with stronger fractal temporal correlations in CoP displacements along AP axes. The attentional demand of the TMT did not affect angular variation or strength of fractal temporal correlations across the 2Dsupport surface. However, maintaining upright balance on the wobble board reshaped and reoriented the angular distribution of fractal temporal correlations, accentuating saddle-like angular variation and rotating the strongest fractal temporal correlations predominantly along the ML axis. Stabilizing posture in the face of wobble board instability prompted the saddle-type angular distribution of fractal temporal correlations. These findings challenge the traditional dependence of postural control theories exclusively on external force-plate axes and underscore the significance of multifractality in defining control parameters that govern postural stability across the full angular range of the 2D support surface.
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Affiliation(s)
- Brian Schlattmann
- Department of Biomechanics, Center for Research in Human Movement Variability, Division of Biomechanics and Research Development, University of Nebraska at Omaha, Omaha, NE68182, USA
| | - Ken Kiyono
- Graduate School of Engineering Science, Osaka University, Osaka560-8531, Japan
| | - Damian G. Kelty-Stephen
- Department of Psychology, State University of New York at New Paltz, New Paltz, NY12561, USA
| | - Madhur Mangalam
- Department of Biomechanics, Center for Research in Human Movement Variability, Division of Biomechanics and Research Development, University of Nebraska at Omaha, Omaha, NE68182, USA
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Jang Y, Kim H, Oh J. An Array of Carbon Nanofiber Bundle_Based 3D In Vitro Intestinal Microvilli for Mimicking Functional and Physical Activities of the Small Intestine. SMALL (WEINHEIM AN DER BERGSTRASSE, GERMANY) 2024; 20:e2404842. [PMID: 39212639 DOI: 10.1002/smll.202404842] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/13/2024] [Revised: 08/12/2024] [Indexed: 09/04/2024]
Abstract
Researchers have developed in vitro small intestine models of biomimicking microvilli, such as gut-on-a-chip devices. However, fabrication methods developed to date for 2D and 3D in vitro gut still have unsolved limitations. In this study, an innovative fabrication method of a 3D in vitro gut model is introduced for effective drug screening. The villus is formed on a patterned carbon nanofiber (CNF) bundle as a flexible and biocompatible scaffold. Mechanical properties of the fabricated villi structure are investigates. A microfluidic system is applied to induce the movement of CNFs villi. F-actin and Occludin staining of Caco-2 cells on a 2D flat-chip as a control and a 3D gut-chip with or without fluidic stress is observed. A permeability test of FD20 is performed. The proposed 3D gut-chip with fluidic stress achieve the highest value of Papp. Mechano-active stimuli caused by distinct structural and movement effects of CNFs villi as well as stiffness of the suggested CNFs villi not only can help accelerate cell differentiation but also can improve permeability. The proposed 3D gut-chip system further strengthens the potential of the platform to increase the accuracy of various drug tests.
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Affiliation(s)
- Yeongseok Jang
- Department of Mechanical Design Engineering, Jeonbuk National University, Jeonju-si, Jeollabuk-do, 54896, Republic of Korea
- Division of Engineering in Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Cambridge, MA, 02139, USA
| | - Hyojae Kim
- Center for Social Innovation Policy, Office of S&T Policy Planning, Korea Institute of S&T Evaluation and Planning, Eumseong, 27740, Republic of Korea
| | - Jonghyun Oh
- Department of Nano-Bio Mechanical System Engineering, Jeonbuk National University, Jeonju-si, Jeollabuk-do, 54896, Republic of Korea
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6
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Jonassen TM, Imsland AKD, Pittman K. The Effect of Stress on the Skin Welfare of Lumpfish ( Cyclopterus lumpus Linnaeus, 1758) Broodstock. Animals (Basel) 2024; 14:3114. [PMID: 39518837 PMCID: PMC11545186 DOI: 10.3390/ani14213114] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2024] [Revised: 10/22/2024] [Accepted: 10/26/2024] [Indexed: 11/16/2024] Open
Abstract
The aim of this study was to build on the work already conducted in optimising lumpfish broodstock temperature, photoperiod and nutrition by providing vital information on the stress relationship between mucosal barrier functions and the sexual development of lumpfish broodstock. From a population of approx. 300 fish of 1587 g (SEM ± 704 g), a sub-population of 20 fish was injected with 30 mg/kg fish cortisol implants on 5 January 2018. The control group was not treated with implants. The stress-induced cortisol implant group showed elevated plasma cortisol over a period of approximately one month. Analyses of mucus cell area and density suggested that induced stress could produce a positive functional response (stimulus) in lumpfish early in the experiment through a gentle increase in the barrier strength of the skin, reduced mucus cell size and increased density of mucous cells, resulting in a strengthening of the respiratory capacity of the gills. Mucous cell density and calculated barrier strength in the skin were significantly negatively correlated with plasma cortisol, while in the gill filaments of females, there was a significant negative correlation between mucous cell density and oestrogen levels. The reduced density of "empty" cells (Q cells) after stress induction indicates that these cells are important for the maintenance of homeostasis (physiological equilibrium). The fish in this experiment were considered more robust compared to previous analyses on smaller lumpfish.
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Affiliation(s)
| | - Albert Kjartan Dagbjartarson Imsland
- Akvaplan-niva AS, Iceland Office, Akralind 6, 201 Kópavogur, Iceland
- Department of Biological Sciences, University of Bergen, High Technology Centre, 5020 Bergen, Norway;
| | - Karin Pittman
- Department of Biological Sciences, University of Bergen, High Technology Centre, 5020 Bergen, Norway;
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Zou J, Peng B, Fan N, Liu Y. Simulation and experimental study on the influence of lamina on nanoneedle penetration into the cell nucleus. Biomech Model Mechanobiol 2024; 23:1241-1262. [PMID: 38526703 DOI: 10.1007/s10237-024-01836-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2023] [Accepted: 02/21/2024] [Indexed: 03/27/2024]
Abstract
We have developed a finite element model to simulate the penetration of nanoneedles into the cellular nucleus. It is found that the nuclear lamina, the primary supporting structure of the nuclear membrane, plays a crucial role in maintaining the integrity of the nuclear envelope and enhancing stress concentration in the nuclear membrane. Notably, nuclear lamina A exhibits a more pronounced effect compared to nuclear lamina B. Subsequently, we further conducted experiments by controlling the time of osteopontin (OPN) treatment to modify the nuclear lamina density, and the results showed that an increase in nuclear lamina density enhances the probability of nanoneedle penetration into the nuclear membrane. Through employing both simulation and experimental techniques, we have gathered compelling evidence indicating that an augmented density of nuclear lamina A can enhance the penetration of nanoneedles into the nuclear membrane.
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Affiliation(s)
- Jie Zou
- School of Mechatronics Engineering, University of Electronic Science and Technology of China, Chengdu, 611731, China
| | - Bei Peng
- School of Mechatronics Engineering, University of Electronic Science and Technology of China, Chengdu, 611731, China
| | - Na Fan
- School of Mechatronics Engineering, University of Electronic Science and Technology of China, Chengdu, 611731, China.
| | - Yang Liu
- College of Polymer Science and Engineering, State Key Laboratory of Polymer Materials Engineering, Sichuan University, Chengdu, 610065, China.
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8
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Lee KWA, Chan KWL, Lee A, Lee CH, Wan J, Wong S, Yi KH. Polynucleotides in Aesthetic Medicine: A Review of Current Practices and Perceived Effectiveness. Int J Mol Sci 2024; 25:8224. [PMID: 39125793 PMCID: PMC11311621 DOI: 10.3390/ijms25158224] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2024] [Revised: 07/23/2024] [Accepted: 07/25/2024] [Indexed: 08/12/2024] Open
Abstract
Polynucleotides, complex molecules composed of nucleotides, have gained attention in aesthetic medicine for their potential to regulate gene expression and promote tissue regeneration. This review aims to provide an overview of the current practices and perceived effectiveness of polynucleotides in aesthetic medicine. A comprehensive search of the literature was conducted using keywords related to polynucleotides, cosmetic application, and aesthetic application. Studies were selected based on their relevance to aesthetic medicine and the inclusion of human subjects. The review found that polynucleotides have been used to improve skin texture, reduce wrinkle depth, and enhance facial appearance. The studies reported varying degrees of efficacy and safety, with some studies demonstrating significant improvements in skin elasticity and hydration. However, others reported limited or no benefits. The review also highlighted the need for further research to establish the optimal use and efficacy of polynucleotides in aesthetic medicine. While the existing literature suggests that polynucleotides may have potential benefits in aesthetic medicine, more research is needed to fully understand their mechanisms of action and optimal use. Clinicians should be aware of the current limitations and potential risks associated with the use of polynucleotides in aesthetic medicine.
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Affiliation(s)
- Kar Wai Alvin Lee
- EverKeen Medical Centre, Hong Kong; (K.W.A.L.); (K.W.L.C.); (C.H.L.)
| | | | | | - Cheuk Hung Lee
- EverKeen Medical Centre, Hong Kong; (K.W.A.L.); (K.W.L.C.); (C.H.L.)
| | - Jovian Wan
- Asia-Pacific Aesthetic Academy, Hong Kong;
| | - Sky Wong
- Leciel Medical Centre, Hong Kong;
| | - Kyu-Ho Yi
- Division in Anatomy and Developmental Biology, Department of Oral Biology, Human Identification Research Institute, BK21 FOUR Project, Yonsei University College of Dentistry, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of Korea
- Maylin Clinic (Apgujeong), Seoul, Republic of Korea
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Zubiarrain-Laserna A, Martínez-Moreno D, López de Andrés J, de Lara-Peña L, Guaresti O, Zaldua AM, Jiménez G, Marchal JA. Beyond stiffness: deciphering the role of viscoelasticity in cancer evolution and treatment response. Biofabrication 2024; 16:042002. [PMID: 38862006 DOI: 10.1088/1758-5090/ad5705] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2023] [Accepted: 06/11/2024] [Indexed: 06/13/2024]
Abstract
There is increasing evidence that cancer progression is linked to tissue viscoelasticity, which challenges the commonly accepted notion that stiffness is the main mechanical hallmark of cancer. However, this new insight has not reached widespread clinical use, as most clinical trials focus on the application of tissue elasticity and stiffness in diagnostic, therapeutic, and surgical planning. Therefore, there is a need to advance the fundamental understanding of the effect of viscoelasticity on cancer progression, to develop novel mechanical biomarkers of clinical significance. Tissue viscoelasticity is largely determined by the extracellular matrix (ECM), which can be simulatedin vitrousing hydrogel-based platforms. Since the mechanical properties of hydrogels can be easily adjusted by changing parameters such as molecular weight and crosslinking type, they provide a platform to systematically study the relationship between ECM viscoelasticity and cancer progression. This review begins with an overview of cancer viscoelasticity, describing how tumor cells interact with biophysical signals in their environment, how they contribute to tumor viscoelasticity, and how this translates into cancer progression. Next, an overview of clinical trials focused on measuring biomechanical properties of tumors is presented, highlighting the biomechanical properties utilized for cancer diagnosis and monitoring. Finally, this review examines the use of biofabricated tumor models for studying the impact of ECM viscoelasticity on cancer behavior and progression and it explores potential avenues for future research on the production of more sophisticated and biomimetic tumor models, as well as their mechanical evaluation.
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Affiliation(s)
- Ana Zubiarrain-Laserna
- Leartiker S. Coop., Xemein Etorbidea 12A, 48270 Markina-Xemein, Spain
- BioFab i3D- Biofabrication and 3D (bio)printing Laboratory, University of Granada, 18100 Granada, Spain
- Biopathology and Regenerative Medicine Institute (IBIMER), Centre for Biomedical Research, (CIBM) University of Granada, Granada, Spain
| | - Daniel Martínez-Moreno
- BioFab i3D- Biofabrication and 3D (bio)printing Laboratory, University of Granada, 18100 Granada, Spain
- Biopathology and Regenerative Medicine Institute (IBIMER), Centre for Biomedical Research, (CIBM) University of Granada, Granada, Spain
- Instituto de Investigación Biosanitaria de Granada (ibs.GRANADA), Granada, Spain
- Excellence Research Unit 'Modeling Nature' (MNat), University of Granada, Granada, Spain
| | - Julia López de Andrés
- BioFab i3D- Biofabrication and 3D (bio)printing Laboratory, University of Granada, 18100 Granada, Spain
- Biopathology and Regenerative Medicine Institute (IBIMER), Centre for Biomedical Research, (CIBM) University of Granada, Granada, Spain
- Instituto de Investigación Biosanitaria de Granada (ibs.GRANADA), Granada, Spain
- Excellence Research Unit 'Modeling Nature' (MNat), University of Granada, Granada, Spain
- Department of Human Anatomy and Embryology, Faculty of Medicine, University of Granada, Granada, Spain
| | - Laura de Lara-Peña
- BioFab i3D- Biofabrication and 3D (bio)printing Laboratory, University of Granada, 18100 Granada, Spain
- Biopathology and Regenerative Medicine Institute (IBIMER), Centre for Biomedical Research, (CIBM) University of Granada, Granada, Spain
- Instituto de Investigación Biosanitaria de Granada (ibs.GRANADA), Granada, Spain
- Excellence Research Unit 'Modeling Nature' (MNat), University of Granada, Granada, Spain
- Department of Human Anatomy and Embryology, Faculty of Medicine, University of Granada, Granada, Spain
| | - Olatz Guaresti
- Leartiker S. Coop., Xemein Etorbidea 12A, 48270 Markina-Xemein, Spain
| | - Ane Miren Zaldua
- Leartiker S. Coop., Xemein Etorbidea 12A, 48270 Markina-Xemein, Spain
| | - Gema Jiménez
- BioFab i3D- Biofabrication and 3D (bio)printing Laboratory, University of Granada, 18100 Granada, Spain
- Biopathology and Regenerative Medicine Institute (IBIMER), Centre for Biomedical Research, (CIBM) University of Granada, Granada, Spain
- Instituto de Investigación Biosanitaria de Granada (ibs.GRANADA), Granada, Spain
- Excellence Research Unit 'Modeling Nature' (MNat), University of Granada, Granada, Spain
- Department of Health Science, Faculty of Experimental Science, University of Jaen, 23071 Jaen, Spain
| | - Juan Antonio Marchal
- BioFab i3D- Biofabrication and 3D (bio)printing Laboratory, University of Granada, 18100 Granada, Spain
- Biopathology and Regenerative Medicine Institute (IBIMER), Centre for Biomedical Research, (CIBM) University of Granada, Granada, Spain
- Instituto de Investigación Biosanitaria de Granada (ibs.GRANADA), Granada, Spain
- Excellence Research Unit 'Modeling Nature' (MNat), University of Granada, Granada, Spain
- Department of Human Anatomy and Embryology, Faculty of Medicine, University of Granada, Granada, Spain
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Pio-Lopez L, Levin M. Aging as a loss of morphostatic information: A developmental bioelectricity perspective. Ageing Res Rev 2024; 97:102310. [PMID: 38636560 DOI: 10.1016/j.arr.2024.102310] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2023] [Revised: 02/21/2024] [Accepted: 04/12/2024] [Indexed: 04/20/2024]
Abstract
Maintaining order at the tissue level is crucial throughout the lifespan, as failure can lead to cancer and an accumulation of molecular and cellular disorders. Perhaps, the most consistent and pervasive result of these failures is aging, which is characterized by the progressive loss of function and decline in the ability to maintain anatomical homeostasis and reproduce. This leads to organ malfunction, diseases, and ultimately death. The traditional understanding of aging is that it is caused by the accumulation of molecular and cellular damage. In this article, we propose a complementary view of aging from the perspective of endogenous bioelectricity which has not yet been integrated into aging research. We propose a view of aging as a morphostasis defect, a loss of biophysical prepattern information, encoding anatomical setpoints used for dynamic tissue and organ homeostasis. We hypothesize that this is specifically driven by abrogation of the endogenous bioelectric signaling that normally harnesses individual cell behaviors toward the creation and upkeep of complex multicellular structures in vivo. Herein, we first describe bioelectricity as the physiological software of life, and then identify and discuss the links between bioelectricity and life extension strategies and age-related diseases. We develop a bridge between aging and regeneration via bioelectric signaling that suggests a research program for healthful longevity via morphoceuticals. Finally, we discuss the broader implications of the homologies between development, aging, cancer and regeneration and how morphoceuticals can be developed for aging.
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Affiliation(s)
- Léo Pio-Lopez
- Allen Discovery Center, Tufts University, Medford, MA 02155, USA
| | - Michael Levin
- Allen Discovery Center, Tufts University, Medford, MA 02155, USA; Wyss Institute for Biologically Inspired Engineering, Boston, MA 02115, USA.
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11
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Khounsaraki GM, Movahedi M, Oscuii HN, Voloshin A. Analysis of the Adherent Cell Response to the Substrate Stiffness Using Tensegrity. Ann Biomed Eng 2024; 52:1213-1221. [PMID: 38324074 DOI: 10.1007/s10439-024-03447-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2023] [Accepted: 01/09/2024] [Indexed: 02/08/2024]
Abstract
Cell's shape is dependent on the cytoskeleton mechanical properties. Hybrid models were developed that combine the discrete structure for the cytoskeleton and continuum parts for other cell organelles. Tensegrity-based structures that consist of tensile and compression elements are useful models to understand the cytoskeleton mechanical behavior. In this study, we are looking to examine the reaction of the cell to a variety of substrate stiffnesses and explain the relationship between cell behavior and substrate mechanical properties. However, which tensegrity structure is appropriate for modeling a living cell? Is the structure's complexity play a major role? We used two spherical tensegrities with different complexities to assess the impact of the structure on the cell's mechanical response versus substrate's stiffness. Six- and twelve-strut tensegrities together with membrane, cytoplasm, nucleoskeleton, and nucleus envelope were assembled in Abaqus package to create a hybrid cell model. A compressive load was applied to the cell model and the reaction forces versus deflection curves were analyzed for number of substrate stiffness values. By analyzing the difference due to two different tensegrities it became clear that the lower density structure is a better choice for modeling stiffer cells. It was also found that the six-strut tensegrity is sensitive to higher range of substrate stiffness.
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Affiliation(s)
| | | | | | - Arkady Voloshin
- Department of Mechanical Engineering and Mechanics, Lehigh University, Bethlehem, PA, 18017, USA.
- Department of Bioengineering, Lehigh University, Bethlehem, PA, 18017, USA.
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12
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Mangalam M, Seleznov I, Kolosova E, Popov A, Kelty-Stephen DG, Kiyono K. Postural control in gymnasts: anisotropic fractal scaling reveals proprioceptive reintegration in vestibular perturbation. FRONTIERS IN NETWORK PHYSIOLOGY 2024; 4:1393171. [PMID: 38699200 PMCID: PMC11063314 DOI: 10.3389/fnetp.2024.1393171] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 02/28/2024] [Accepted: 04/05/2024] [Indexed: 05/05/2024]
Abstract
Dexterous postural control subtly complements movement variability with sensory correlations at many scales. The expressive poise of gymnasts exemplifies this lyrical punctuation of release with constraint, from coarse grain to fine scales. Dexterous postural control upon a 2D support surface might collapse the variation of center of pressure (CoP) to a relatively 1D orientation-a direction often oriented towards the focal point of a visual task. Sensory corrections in dexterous postural control might manifest in temporal correlations, specifically as fractional Brownian motions whose differences are more and less correlated with fractional Gaussian noises (fGns) with progressively larger and smaller Hurst exponent H. Traditional empirical work examines this arrangement of lower-dimensional compression of CoP along two orthogonal axes, anteroposterior (AP) and mediolateral (ML). Eyes-open and face-forward orientations cultivate greater variability along AP than ML axes, and the orthogonal distribution of spatial variability has so far gone hand in hand with an orthogonal distribution of H, for example, larger in AP and lower in ML. However, perturbing the orientation of task focus might destabilize the postural synergy away from its 1D distribution and homogenize the temporal correlations across the 2D support surface, resulting in narrower angles between the directions of the largest and smallest H. We used oriented fractal scaling component analysis (OFSCA) to investigate whether sensory corrections in postural control might thus become suborthogonal. OFSCA models raw 2D CoP trajectory by decomposing it in all directions along the 2D support surface and fits the directions with the largest and smallest H. We studied a sample of gymnasts in eyes-open and face-forward quiet posture, and results from OFSCA confirm that such posture exhibits the classic orthogonal distribution of temporal correlations. Head-turning resulted in a simultaneous decrease in this angle Δθ, which promptly reversed once gymnasts reoriented their heads forward. However, when vision was absent, there was only a discernible negative trend in Δθ, indicating a shift in the angle's direction but not a statistically significant one. Thus, the narrowing of Δθ may signify an adaptive strategy in postural control. The swift recovery of Δθ upon returning to a forward-facing posture suggests that the temporary reduction is specific to head-turning and does not impose a lasting burden on postural control. Turning the head reduced the angle between these two orientations, facilitating the release of postural degrees of freedom towards a more uniform spread of the CoP across both dimensions of the support surface. The innovative aspect of this work is that it shows how fractality might serve as a control parameter of adaptive mechanisms of dexterous postural control.
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Affiliation(s)
- Madhur Mangalam
- Division of Biomechanics and Research Development, Department of Biomechanics, and Center for Research in Human Movement Variability, University of Nebraska at Omaha, Omaha, NE, United States
| | - Ivan Seleznov
- Graduate School of Engineering Science, Osaka University, Osaka, Japan
| | - Elena Kolosova
- National University of Ukraine on Physical Education and Sport, Scientific Research Institute, Kyiv, Ukraine
- Department of Movement Physiology, Bogomoletz Institute of Physiology, Kyiv, Ukraine
| | - Anton Popov
- Department of Electronic Engineering, Igor Sikorsky Kyiv Polytechnic Institute, Kyiv, Ukraine
- Faculty of Applied Sciences, Ukrainian Catholic University, Lviv, Ukraine
| | - Damian G. Kelty-Stephen
- Department of Psychology, State University of New York at New Paltz, New Paltz, NY, United States
| | - Ken Kiyono
- Graduate School of Engineering Science, Osaka University, Osaka, Japan
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13
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Fernandez-Carro E, Remacha AR, Orera I, Lattanzio G, Garcia-Barrios A, del Barrio J, Alcaine C, Ciriza J. Human Dermal Decellularized ECM Hydrogels as Scaffolds for 3D In Vitro Skin Aging Models. Int J Mol Sci 2024; 25:4020. [PMID: 38612828 PMCID: PMC11011913 DOI: 10.3390/ijms25074020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2024] [Revised: 04/01/2024] [Accepted: 04/02/2024] [Indexed: 04/14/2024] Open
Abstract
Biomaterials play an important role in the development of advancing three dimensional (3D) in vitro skin models, providing valuable insights for drug testing and tissue-specific modeling. Commercial materials, such as collagen, fibrin or alginate, have been widely used in skin modeling. However, they do not adequately represent the molecular complexity of skin components. On this regard, the development of novel biomaterials that represent the complexity of tissues is becoming more important in the design of advanced models. In this study, we have obtained aged human decellularized dermal extracellular matrix (dECM) hydrogels extracted from cadaveric human skin and demonstrated their potential as scaffold for advanced skin models. These dECM hydrogels effectively reproduce the complex fibrillar structure of other common scaffolds, exhibiting similar mechanical properties, while preserving the molecular composition of the native dermis. It is worth noting that fibroblasts embedded within human dECM hydrogels exhibit a behavior more representative of natural skin compared to commercial collagen hydrogels, where uncontrolled cell proliferation leads to material shrinkage. The described human dECM hydrogel is able to be used as scaffold for dermal fibroblasts in a skin aging-on-a-chip model. These results demonstrate that dECM hydrogels preserve essential components of the native human dermis making them a suitable option for the development of 3D skin aging models that accurately represent the cellular microenvironment, improving existing in vitro skin models and allowing for more reliable results in dermatopathological studies.
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Affiliation(s)
- Estibaliz Fernandez-Carro
- Tissue Microenvironment (TME) Lab, Aragón Institute of Engineering Research (I3A), University of Zaragoza, C/Mariano Esquillor s/n, 500018 Zaragoza, Spain; (E.F.-C.); (C.A.)
- Institute for Health Research Aragón (IIS Aragón), Avda. San Juan Bosco, 13, 50009 Zaragoza, Spain
| | - Ana Rosa Remacha
- Tissue Microenvironment (TME) Lab, Aragón Institute of Engineering Research (I3A), University of Zaragoza, C/Mariano Esquillor s/n, 500018 Zaragoza, Spain; (E.F.-C.); (C.A.)
| | - Irene Orera
- Proteomics Research Core Facility, Instituto Aragonés de Ciencias de la Salud (IACS), 50009 Zaragoza, Spain; (I.O.)
| | - Giuseppe Lattanzio
- Proteomics Research Core Facility, Instituto Aragonés de Ciencias de la Salud (IACS), 50009 Zaragoza, Spain; (I.O.)
| | - Alberto Garcia-Barrios
- Department of Anatomy and Histology, Faculty of Medicine, University of Zaragoza, 50009 Zaragoza, Spain
| | - Jesús del Barrio
- Departamento de Química Orgánica, Instituto de Nanociencia y Materiales de Aragón (INMA), CSIC-Universidad de Zaragoza, 50009 Zaragoza, Spain;
| | - Clara Alcaine
- Tissue Microenvironment (TME) Lab, Aragón Institute of Engineering Research (I3A), University of Zaragoza, C/Mariano Esquillor s/n, 500018 Zaragoza, Spain; (E.F.-C.); (C.A.)
- Institute for Health Research Aragón (IIS Aragón), Avda. San Juan Bosco, 13, 50009 Zaragoza, Spain
| | - Jesús Ciriza
- Tissue Microenvironment (TME) Lab, Aragón Institute of Engineering Research (I3A), University of Zaragoza, C/Mariano Esquillor s/n, 500018 Zaragoza, Spain; (E.F.-C.); (C.A.)
- Institute for Health Research Aragón (IIS Aragón), Avda. San Juan Bosco, 13, 50009 Zaragoza, Spain
- Department of Anatomy and Histology, Faculty of Medicine, University of Zaragoza, 50009 Zaragoza, Spain
- Centro de Investigación Biomédica en Red en Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), 28029 Madrid, Spain
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14
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Kim MJ, Park H, Jung R, Won C, Ohk S, Kim H, Roh N, Yi K. High-resolution 3-D scanning electron microscopy (SEM) images of DOT TM polynucleotides (PN): Unique scaffold characteristics and potential applications in biomedicine. Skin Res Technol 2024; 30:e13667. [PMID: 38558437 PMCID: PMC10982675 DOI: 10.1111/srt.13667] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2024] [Accepted: 03/11/2024] [Indexed: 04/04/2024]
Abstract
INTRODUCTION Polynucleotides (PN) are becoming more prominent in aesthetic medicine. However, the structural characteristics of PN have not been published and PN from different companies may have different structural characteristics. This study aimed to elucidate the structural attributes of DOT™ PN and distinguish differences with polydeoxyribonucleotides (PDRN) using high-resolution scanning electron microscopy (SEM) imaging. MATERIALS AND METHODS DOT™ PN was examined using a Quanta 3-D field emission gun (FEG) Scanning Electron Microscope (SEM). Sample preparation involved cryogenic cooling, cleavage, etching, and metal coating to facilitate high-resolution imaging. Cryo-FIB/SEM techniques were employed for in-depth structural analysis. RESULTS PDRN exhibited an amorphous structure without distinct features. In contrast, DOT™ PN displayed well-defined polyhedral shapes with smooth, uniformly thick walls. These cells were empty, with diameters ranging from 3 to 8 micrometers, forming a seamless tessellation pattern. DISCUSSION DOT™ PN's distinct geometric tessellation design conforms to the principles of biotensegrity, providing both structural reinforcement and integrity. The presence of delicate partitions and vacant compartments hints at possible uses in the field of pharmaceutical delivery systems. Within the realms of beauty enhancement and regenerative medicine, DOT™ PN's capacity to bolster cell growth and tissue mending could potentially transform approaches to rejuvenation treatments. Its adaptability becomes apparent when considering its contributions to drug administration and surgical procedures. CONCLUSION This study unveils the intricate structural scaffold features of DOT™ PN for the first time, setting it apart from PDRN and inspiring innovation in biomedicine and materials science. DOT™ PN's unique attributes open doors to potential applications across healthcare and beyond.
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Affiliation(s)
| | | | - Rae‐Jun Jung
- Pharmaresearch Co., Ltd. Integrated R&D CenterSungnamSouth Korea
| | - Chee‐Youb Won
- Pharmaresearch Co., Ltd. Integrated R&D CenterSungnamSouth Korea
| | - Seul‐Ong Ohk
- Pharmaresearch Co., Ltd. Integrated R&D CenterSungnamSouth Korea
| | - Hong‐Taek Kim
- Pharmaresearch Co., Ltd. Integrated R&D CenterSungnamSouth Korea
| | - Nark‐Kyung Roh
- Leaders Aesthetic Laser and Cosmetic Surgery CenterSeoulSouth Korea
| | - Kyu‐Ho Yi
- Maylin Clinic (Apgujeong)SeoulSouth Korea
- Division in Anatomy and Developmental BiologyDepartment of Oral BiologyHuman Identification Research InstituteBK21 FOUR ProjectYonsei University College of DentistrySeoulSouth Korea
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15
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Shu J, Deng H, Zhang Y, Wu F, He J. Cancer cell response to extrinsic and intrinsic mechanical cue: opportunities for tumor apoptosis strategies. Regen Biomater 2024; 11:rbae016. [PMID: 38476678 PMCID: PMC10932484 DOI: 10.1093/rb/rbae016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2023] [Revised: 01/31/2024] [Accepted: 02/07/2024] [Indexed: 03/14/2024] Open
Abstract
Increasing studies have revealed the importance of mechanical cues in tumor progression, invasiveness and drug resistance. During malignant transformation, changes manifest in either the mechanical properties of the tissue or the cellular ability to sense and respond to mechanical signals. The major focus of the review is the subtle correlation between mechanical cues and apoptosis in tumor cells from a mechanobiology perspective. To begin, we focus on the intracellular force, examining the mechanical properties of the cell interior, and outlining the role that the cytoskeleton and intracellular organelle-mediated intracellular forces play in tumor cell apoptosis. This article also elucidates the mechanisms by which extracellular forces guide tumor cell mechanosensing, ultimately triggering the activation of the mechanotransduction pathway and impacting tumor cell apoptosis. Finally, a comprehensive examination of the present status of the design and development of anti-cancer materials targeting mechanotransduction is presented, emphasizing the underlying design principles. Furthermore, the article underscores the need to address several unresolved inquiries to enhance our comprehension of cancer therapeutics that target mechanotransduction.
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Affiliation(s)
- Jun Shu
- National Engineering Research Center for Biomaterials, College of Biomedical Engineering, Sichuan University, Chengdu 610064, PR China
| | - Huan Deng
- National Engineering Research Center for Biomaterials, College of Biomedical Engineering, Sichuan University, Chengdu 610064, PR China
| | - Yu Zhang
- College of Food and Biological Engineering, Chengdu University, Chengdu 610106, PR China
| | - Fang Wu
- National Engineering Research Center for Biomaterials, College of Biomedical Engineering, Sichuan University, Chengdu 610064, PR China
| | - Jing He
- National Engineering Research Center for Biomaterials, College of Biomedical Engineering, Sichuan University, Chengdu 610064, PR China
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16
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Li W, Li A, Yu B, Zhang X, Liu X, White KL, Stevens RC, Baumeister W, Sali A, Jasnin M, Sun L. In situ structure of actin remodeling during glucose-stimulated insulin secretion using cryo-electron tomography. Nat Commun 2024; 15:1311. [PMID: 38346988 PMCID: PMC10861521 DOI: 10.1038/s41467-024-45648-7] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2023] [Accepted: 01/30/2024] [Indexed: 02/15/2024] Open
Abstract
Actin mediates insulin secretion in pancreatic β-cells through remodeling. Hampered by limited resolution, previous studies have offered an ambiguous depiction as depolymerization and repolymerization. We report the in situ structure of actin remodeling in INS-1E β-cells during glucose-stimulated insulin secretion at nanoscale resolution. After remodeling, the actin filament network at the cell periphery exhibits three marked differences: 12% of actin filaments reorient quasi-orthogonally to the ventral membrane; the filament network mainly remains as cell-stabilizing bundles but partially reconfigures into a less compact arrangement; actin filaments anchored to the ventral membrane reorganize from a "netlike" to a "blooming" architecture. Furthermore, the density of actin filaments and microtubules around insulin secretory granules decreases, while actin filaments and microtubules become more densely packed. The actin filament network after remodeling potentially precedes the transport and release of insulin secretory granules. These findings advance our understanding of actin remodeling and its role in glucose-stimulated insulin secretion.
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Affiliation(s)
- Weimin Li
- iHuman Institute, ShanghaiTech University, Shanghai, 201210, China
- School of Life Science and Technology, ShanghaiTech University, Shanghai, 201210, China
| | - Angdi Li
- iHuman Institute, ShanghaiTech University, Shanghai, 201210, China
- School of Life Science and Technology, ShanghaiTech University, Shanghai, 201210, China
| | - Bing Yu
- iHuman Institute, ShanghaiTech University, Shanghai, 201210, China
- School of Life Science and Technology, ShanghaiTech University, Shanghai, 201210, China
| | - Xiaoxiao Zhang
- iHuman Institute, ShanghaiTech University, Shanghai, 201210, China
| | - Xiaoyan Liu
- iHuman Institute, ShanghaiTech University, Shanghai, 201210, China
| | - Kate L White
- Department of Chemistry, Bridge Institute, USC Michelson Center for Convergent Bioscience, University of Southern California, Los Angeles, CA, 90089, USA
| | - Raymond C Stevens
- iHuman Institute, ShanghaiTech University, Shanghai, 201210, China
- School of Life Science and Technology, ShanghaiTech University, Shanghai, 201210, China
| | - Wolfgang Baumeister
- iHuman Institute, ShanghaiTech University, Shanghai, 201210, China.
- Department of Molecular Structural Biology, Max Planck Institute of Biochemistry, 82152, Martinsried, Germany.
| | - Andrej Sali
- Quantitative Biosciences Institute, University of California, San Francisco, San Francisco, CA, 94158, USA.
- Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA, 94158, USA.
- Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA, 94158, USA.
| | - Marion Jasnin
- Helmholtz Pioneer Campus, Helmholtz Zentrum München, 85764, Neuherberg, Germany.
- Department of Chemistry, Technical University of Munich, 85748, Garching, Germany.
| | - Liping Sun
- iHuman Institute, ShanghaiTech University, Shanghai, 201210, China.
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17
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dos Santos Amorim M, Sinhorim L, Baptistella do Nascimento I, Wagner J, de Paula Lemos F, Duarte França ME, Schleip R, Sonza A, Moraes Santos G. Peripheral muscle oxygenation, pain, and disability indices in individuals with and without nonspecific neck pain, before and after myofascial reorganization®: A double-blind randomized controlled trial. PLoS One 2024; 19:e0292114. [PMID: 38335169 PMCID: PMC10857696 DOI: 10.1371/journal.pone.0292114] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2022] [Accepted: 09/12/2023] [Indexed: 02/12/2024] Open
Abstract
To investigate whether myofascial reorganization® in the trapezius muscle (MRT) improves peripheral muscle oxygenation and pain tolerance and decreases neck disability index (NDI) scores in individuals with and without nonspecific neck pain (NP) using a double-blind randomized controlled trial. Seventy-five subjects were equally and randomly assigned to three groups: the intervention groups (experimental [EG] and sham sSG]) and the control group (CG). Several inclusion criteria were applied to the intervention groups: male or female, aged 18-32 years, self-reported NP in the last 3 months without a defined cause; at least "soft" pain in session 1 of the NDI, and at least a score of 1 on the Visual Analogue Scale (VAS). The CG was required to have NDI and VAS scores of 0 at recruitment. Intervention: The EG underwent MRT for 10 min, once a week for 6 weeks. Patients with NP in the SG underwent classical massage for the same duration and frequency. Patients in the CG had no pain and underwent no intervention. Data collection was performed using the NDI Questionnaire, a pressure algometer for pain evaluation, and near-infrared spectroscopy for muscle oxygenation measurements. It was registered as NCT03882515 at ClinicalTrials.gov. The NDI score in both the EG (p<0.001) and SG (p<0.001) decreased after 6 weeks of intervention compared to the CG. The CG demonstrated a lower basal tissue saturation (TSI) index than the EG (p<0.001) and SG (p = 0.02). The EG demonstrated higher oxyhemoglobin values than the SG (p<0.001) and CG (p = 0.03). The CG had higher pain tolerance than the EG (p = 0.01) and SG (p<0.001) post-intervention. MRT increased trapezius muscle oxygenation after 6 weeks of intervention.
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Affiliation(s)
- Mayane dos Santos Amorim
- College of Health Sciences and Sports at Santa Catarina State University (UDESC), Posture and Balance Laboratory (LAPEQ), Florianópolis, State of Santa Catarina, Brazil
| | - Larissa Sinhorim
- College of Health Sciences and Sports at Santa Catarina State University (UDESC), Posture and Balance Laboratory (LAPEQ), Florianópolis, State of Santa Catarina, Brazil
| | - Iramar Baptistella do Nascimento
- College of Health Sciences and Sports at Santa Catarina State University (UDESC), Posture and Balance Laboratory (LAPEQ), Florianópolis, State of Santa Catarina, Brazil
| | - Janaína Wagner
- College of Health Sciences and Sports at Santa Catarina State University (UDESC), Posture and Balance Laboratory (LAPEQ), Florianópolis, State of Santa Catarina, Brazil
| | - Francisco de Paula Lemos
- College of Health Sciences and Sports at Santa Catarina State University (UDESC), Posture and Balance Laboratory (LAPEQ), Florianópolis, State of Santa Catarina, Brazil
| | - Maria Elisa Duarte França
- College of Health Sciences and Sports at Santa Catarina State University (UDESC), Posture and Balance Laboratory (LAPEQ), Florianópolis, State of Santa Catarina, Brazil
| | - Robert Schleip
- Associate Professorship of Conservative and Rehabilitative Orthopaedics, Department of Sport and Health Sciences, Technical University of Munich, Munich, Germany
- DIPLOMA Hochschule Bad Sooden-Allendorf, Bad Sooden-Allendorf, Germany
| | - Anelise Sonza
- College of Health Sciences and Sports at Santa Catarina State University (UDESC), Posture and Balance Laboratory (LAPEQ), Florianópolis, State of Santa Catarina, Brazil
| | - Gilmar Moraes Santos
- College of Health Sciences and Sports at Santa Catarina State University (UDESC), Posture and Balance Laboratory (LAPEQ), Florianópolis, State of Santa Catarina, Brazil
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18
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Loescher CM, Linke WA. Titin takes centerstage among cytoskeletal contributions to myocardial passive stiffness. Cytoskeleton (Hoboken) 2024; 81:184-187. [PMID: 38158587 DOI: 10.1002/cm.21827] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2023] [Accepted: 12/20/2023] [Indexed: 01/03/2024]
Abstract
Both diastolic filling and systolic pumping of the heart are dependent on the passive stiffness characteristics of various mechanical elements of myocardium. However, the specific contribution from each element, including the extracellular matrix, actin filaments, microtubules, desmin intermediate filaments, and sarcomeric titin springs, remains challenging to assess. Recently, a mouse model allowing for precise and acute cleavage of the titin springs was used to remove one mechanical element after the other from cardiac fibers and record the effect on passive stiffness. It became clear that the stiffness contribution from each element is context-dependent and varies depending on strain level and the force component considered (elastic or viscous); elements do not act in isolation but in a tensegral relationship. Titin is a substantial contributor under all conditions and dominates the elastic forces at both low and high strains. The contribution to viscous forces is more equally shared between microtubules, titin, and actin. However, the extracellular matrix substantially contributes to both force components at higher strain levels. Desmin filaments may bear low stiffness. These insights enhance our understanding of how different filament networks contribute to passive stiffness in the heart and offer new perspectives for targeting this stiffness in heart failure treatment.
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Affiliation(s)
| | - Wolfgang A Linke
- Institute of Physiology II, University of Muenster, Muenster, Germany
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19
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Mei H, Li Z, Lv Q, Li X, Wu Y, Feng Q, Jiang Z, Zhou Y, Zheng Y, Gao Z, Zhou J, Jiang C, Huang S, Li J. Sema3A secreted by sensory nerve induces bone formation under mechanical loads. Int J Oral Sci 2024; 16:5. [PMID: 38238300 PMCID: PMC10796360 DOI: 10.1038/s41368-023-00269-6] [Citation(s) in RCA: 9] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2023] [Revised: 12/19/2023] [Accepted: 12/19/2023] [Indexed: 01/22/2024] Open
Abstract
Bone formation and deposition are initiated by sensory nerve infiltration in adaptive bone remodeling. Here, we focused on the role of Semaphorin 3A (Sema3A), expressed by sensory nerves, in mechanical loads-induced bone formation and nerve withdrawal using orthodontic tooth movement (OTM) model. Firstly, bone formation was activated after the 3rd day of OTM, coinciding with a decrease in sensory nerves and an increase in pain threshold. Sema3A, rather than nerve growth factor (NGF), highly expressed in both trigeminal ganglion and the axons of periodontal ligament following the 3rd day of OTM. Moreover, in vitro mechanical loads upregulated Sema3A in neurons instead of in human periodontal ligament cells (hPDLCs) within 24 hours. Furthermore, exogenous Sema3A restored the suppressed alveolar bone formation and the osteogenic differentiation of hPDLCs induced by mechanical overload. Mechanistically, Sema3A prevented overstretching of F-actin induced by mechanical overload through ROCK2 pathway, maintaining mitochondrial dynamics as mitochondrial fusion. Therefore, Sema3A exhibits dual therapeutic effects in mechanical loads-induced bone formation, both as a pain-sensitive analgesic and a positive regulator for bone formation.
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Affiliation(s)
- Hongxiang Mei
- State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Zhengzheng Li
- State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Qinyi Lv
- State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Xingjian Li
- State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Yumeng Wu
- State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Qingchen Feng
- State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Zhishen Jiang
- State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Yimei Zhou
- State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Yule Zheng
- State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Ziqi Gao
- State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Jiawei Zhou
- State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Chen Jiang
- State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Shishu Huang
- Department of Orthopedic Surgery and Orthopedic Research Institute, West China Hospital, Sichuan University, Chengdu, China.
| | - Juan Li
- State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & West China Hospital of Stomatology, Sichuan University, Chengdu, China.
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20
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Yang J, Barrila J, Nauman EA, Nydam SD, Yang S, Park J, Gutierrez-Jensen AD, Castro CL, Ott CM, Buss K, Steel J, Zakrajsek AD, Schuff MM, Nickerson CA. Incremental increases in physiological fluid shear progressively alter pathogenic phenotypes and gene expression in multidrug resistant Salmonella. Gut Microbes 2024; 16:2357767. [PMID: 38783686 PMCID: PMC11135960 DOI: 10.1080/19490976.2024.2357767] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/20/2024] [Accepted: 05/15/2024] [Indexed: 05/25/2024] Open
Abstract
The ability of bacteria to sense and respond to mechanical forces has important implications for pathogens during infection, as they experience wide fluid shear fluctuations in the host. However, little is known about how mechanical forces encountered in the infected host drive microbial pathogenesis. Herein, we combined mathematical modeling with hydrodynamic bacterial culture to profile transcriptomic and pathogenesis-related phenotypes of multidrug resistant S. Typhimurium (ST313 D23580) under different fluid shear conditions relevant to its transition from the intestinal tract to the bloodstream. We report that D23580 exhibited incremental changes in transcriptomic profiles that correlated with its pathogenic phenotypes in response to these progressive increases in fluid shear. This is the first demonstration that incremental changes in fluid shear forces alter stress responses and gene expression in any ST313 strain and offers mechanistic insight into how forces encountered by bacteria during infection might impact their disease-causing ability in unexpected ways.
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Affiliation(s)
- Jiseon Yang
- Biodesign Center for Fundamental and Applied Microbiomics, Arizona State University, Tempe, AZ, USA
- Biodesign Center for Immunotherapy, Vaccines and Virotherapy, Arizona State University, Tempe, AZ, USA
- School of Life Sciences, Arizona State University, Tempe, AZ, USA
| | - Jennifer Barrila
- Biodesign Center for Fundamental and Applied Microbiomics, Arizona State University, Tempe, AZ, USA
- Biodesign Center for Immunotherapy, Vaccines and Virotherapy, Arizona State University, Tempe, AZ, USA
| | - Eric A. Nauman
- Department of Biomedical Engineering, University of Cincinnati, Cincinnati, OH, USA
| | - Seth D. Nydam
- Department of Animal Care & Technologies, Arizona State University, Tempe, AZ, USA
| | - Shanshan Yang
- Bioinformatics Core Facility, Bioscience, Knowledge Enterprise, Arizona State University, Tempe, AZ, USA
| | - Jin Park
- Biodesign Center for Personalized Diagnostics, Arizona State University, Tempe, AZ, USA
| | - Ami D. Gutierrez-Jensen
- Biodesign Center for Immunotherapy, Vaccines and Virotherapy, Arizona State University, Tempe, AZ, USA
- School of Life Sciences, Arizona State University, Tempe, AZ, USA
| | - Christian L. Castro
- Biodesign Center for Immunotherapy, Vaccines and Virotherapy, Arizona State University, Tempe, AZ, USA
- School of Life Sciences, Arizona State University, Tempe, AZ, USA
- JES Tech, Houston, TX, USA
| | - C. Mark Ott
- Biomedical Research and Environmental Sciences Division, NASA Johnson Space Center, Houston, TX, USA
| | - Kristina Buss
- Bioinformatics Core Facility, Bioscience, Knowledge Enterprise, Arizona State University, Tempe, AZ, USA
- Biodesign Center for Personalized Diagnostics, Arizona State University, Tempe, AZ, USA
| | - Jason Steel
- Bioinformatics Core Facility, Bioscience, Knowledge Enterprise, Arizona State University, Tempe, AZ, USA
- Biodesign Center for Personalized Diagnostics, Arizona State University, Tempe, AZ, USA
| | - Anne D. Zakrajsek
- Department of Biomedical Engineering, University of Cincinnati, Cincinnati, OH, USA
| | - Mary M. Schuff
- Department of Biomedical Engineering, University of Cincinnati, Cincinnati, OH, USA
| | - Cheryl A. Nickerson
- Biodesign Center for Fundamental and Applied Microbiomics, Arizona State University, Tempe, AZ, USA
- Biodesign Center for Immunotherapy, Vaccines and Virotherapy, Arizona State University, Tempe, AZ, USA
- School of Life Sciences, Arizona State University, Tempe, AZ, USA
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21
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Loescher CM, Freundt JK, Unger A, Hessel AL, Kühn M, Koser F, Linke WA. Titin governs myocardial passive stiffness with major support from microtubules and actin and the extracellular matrix. NATURE CARDIOVASCULAR RESEARCH 2023; 2:991-1002. [PMID: 39196092 PMCID: PMC11358001 DOI: 10.1038/s44161-023-00348-1] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/07/2023] [Accepted: 09/19/2023] [Indexed: 08/29/2024]
Abstract
Myocardial passive stiffness is crucial for the heart's pump function and is determined by mechanical elements, including the extracellular matrix and cytoskeletal filaments; however, their individual contributions are controversially discussed and difficult to quantify. In this study, we targeted the cytoskeletal filaments in a mouse model, which enables the specific, acute and complete cleavage of the sarcomeric titin springs. We show in vitro that each cytoskeletal filament's stiffness contribution varies depending on whether the elastic or the viscous forces are considered and on strain level. Titin governs myocardial elastic forces, with the largest contribution provided at both low and high strain. Viscous force contributions are more uniformly distributed among the microtubules, titin and actin. The extracellular matrix contributes at high strain. The remaining forces after total target element disruption are likely derived from desmin filaments. Our findings answer longstanding questions about cardiac mechanical architecture and allow better targeting of passive myocardial stiffness in heart failure.
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Affiliation(s)
| | - Johanna K Freundt
- Institute of Physiology II, University of Muenster, Muenster, Germany
| | - Andreas Unger
- Institute of Physiology II, University of Muenster, Muenster, Germany
| | - Anthony L Hessel
- Institute of Physiology II, University of Muenster, Muenster, Germany
| | - Michel Kühn
- Institute of Physiology II, University of Muenster, Muenster, Germany
| | - Franziska Koser
- Institute of Physiology II, University of Muenster, Muenster, Germany
| | - Wolfgang A Linke
- Institute of Physiology II, University of Muenster, Muenster, Germany.
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22
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Salvarani N, Peretto G, Silvia C, Villatore A, Thairi C, Santoni A, Galli C, Carrera P, Sala S, Benedetti S, Di Pasquale E, Di Resta C. Functional Characterisation of the Rare SCN5A p.E1225K Variant, Segregating in a Brugada Syndrome Familial Case, in Human Cardiomyocytes from Pluripotent Stem Cells. Int J Mol Sci 2023; 24:ijms24119548. [PMID: 37298497 DOI: 10.3390/ijms24119548] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2023] [Revised: 05/18/2023] [Accepted: 05/25/2023] [Indexed: 06/12/2023] Open
Abstract
Brugada syndrome (BrS) is an inherited autosomal dominant cardiac channelopathy. Pathogenic rare mutations in the SCN5A gene, encoding the alpha-subunit of the voltage-dependent cardiac Na+ channel protein (Nav1.5), are identified in 20% of BrS patients, affecting the correct function of the channel. To date, even though hundreds of SCN5A variants have been associated with BrS, the underlying pathogenic mechanisms are still unclear in most cases. Therefore, the functional characterization of the SCN5A BrS rare variants still represents a major hurdle and is fundamental to confirming their pathogenic effect. Human cardiomyocytes (CMs) differentiated from pluripotent stem cells (PSCs) have been extensively demonstrated to be reliable platforms for investigating cardiac diseases, being able to recapitulate specific traits of disease, including arrhythmic events and conduction abnormalities. Based on this, in this study, we performed a functional analysis of the BrS familial rare variant NM_198056.2:c.3673G>A (NP_932173.1:p.Glu1225Lys), which has been never functionally characterized before in a cardiac-relevant context, as the human cardiomyocyte. Using a specific lentiviral vector encoding a GFP-tagged SCN5A gene carrying the specific c.3673G>A variant and CMs differentiated from control PSCs (PSC-CMs), we demonstrated an impairment of the mutated Nav1.5, thus suggesting the pathogenicity of the rare BrS detected variant. More broadly, our work supports the application of PSC-CMs for the assessment of the pathogenicity of gene variants, the identification of which is increasing exponentially due to the advances in next-generation sequencing methods and their massive use in genetic testing.
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Affiliation(s)
- Nicolò Salvarani
- Institute of Genetic and Biomedical Research (IRGB), UOS of Milan, National Research Council of Italy, 20138 Milan, Italy
- IRCCS Humanitas Research Hospital, Via Manzoni 56, Rozzano, 20089 Milan, Italy
| | - Giovanni Peretto
- Department of Cardiac Electrophysiology and Arrhythmology, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy
- Faculty of Medicine, Vita-Salute San Raffaele University, 20132 Milan, Italy
| | - Crasto Silvia
- IRCCS Humanitas Research Hospital, Via Manzoni 56, Rozzano, 20089 Milan, Italy
| | - Andrea Villatore
- Faculty of Medicine, Vita-Salute San Raffaele University, 20132 Milan, Italy
| | - Cecilia Thairi
- IRCCS Humanitas Research Hospital, Via Manzoni 56, Rozzano, 20089 Milan, Italy
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, Pieve Emanuele, 20072 Milan, Italy
| | - Anna Santoni
- Genomic Unit for the Diagnosis of Human Pathologies, IRCCS San Raffaele Hospital, 20132 Milan, Italy
| | - Camilla Galli
- IRCCS Humanitas Research Hospital, Via Manzoni 56, Rozzano, 20089 Milan, Italy
| | - Paola Carrera
- Genomic Unit for the Diagnosis of Human Pathologies, IRCCS San Raffaele Hospital, 20132 Milan, Italy
- Laboratory of Clinical Molecular Biology, IRCCS San Raffaele Hospital, 20132 Milan, Italy
| | - Simone Sala
- Department of Cardiac Electrophysiology and Arrhythmology, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy
| | - Sara Benedetti
- Genomic Unit for the Diagnosis of Human Pathologies, IRCCS San Raffaele Hospital, 20132 Milan, Italy
| | - Elisa Di Pasquale
- Institute of Genetic and Biomedical Research (IRGB), UOS of Milan, National Research Council of Italy, 20138 Milan, Italy
- IRCCS Humanitas Research Hospital, Via Manzoni 56, Rozzano, 20089 Milan, Italy
| | - Chiara Di Resta
- Faculty of Medicine, Vita-Salute San Raffaele University, 20132 Milan, Italy
- Genomic Unit for the Diagnosis of Human Pathologies, IRCCS San Raffaele Hospital, 20132 Milan, Italy
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23
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Odagiri K, Fujisaki H, Takada H, Ogawa R. Mathematical model for promotion of wound closure with ATP release. Biophys Physicobiol 2023; 20:e200023. [PMID: 38496238 PMCID: PMC10941958 DOI: 10.2142/biophysico.bppb-v20.0023] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2022] [Accepted: 05/22/2023] [Indexed: 03/19/2024] Open
Abstract
To computationally investigate the recent experimental finding such that extracellular ATP release caused by exogeneous mechanical forces promote wound closure, we introduce a mathematical model, the Cellular Potts Model (CPM), which is a popular discretized model on a lattice, where the movement of a "cell" is determined by a Monte Carlo procedure. In the experiment, it was observed that there is mechanosensitive ATP release from the leading cells facing the wound gap and the subsequent extracellular Ca2+ influx. To model these phenomena, the Reaction-Diffusion equations for extracellular ATP and intracellular Ca2+ concentrations are adopted and combined with CPM, where we also add a polarity term because the cell migration is enhanced in the case of ATP release. From the numerical simulations using this hybrid model, we discuss effects of the collective cell migration due to the ATP release and the Ca2+ influx caused by the mechanical forces and the consequent promotion of wound closure.
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Affiliation(s)
- Kenta Odagiri
- School of Network and Information, Senshu University, Kawasaki, Kanagawa 214-8580, Japan
- AMED-CREST, Bunkyo, Tokyo 113-8603, Japan
| | - Hiroshi Fujisaki
- AMED-CREST, Bunkyo, Tokyo 113-8603, Japan
- Department of Physics, Nippon Medical School, Musashino, Tokyo 180-0023, Japan
| | - Hiroya Takada
- AMED-CREST, Bunkyo, Tokyo 113-8603, Japan
- Department of Anti-Aging and Preventive Medicine, Nippon Medical School, Bunkyo, Tokyo 113-8603, Japan
- Department of Plastic, Reconstructive and Aesthetic Surgery, Nippon Medical School, Bunkyo, Tokyo 113-8603, Japan
| | - Rei Ogawa
- AMED-CREST, Bunkyo, Tokyo 113-8603, Japan
- Department of Plastic, Reconstructive and Aesthetic Surgery, Nippon Medical School, Bunkyo, Tokyo 113-8603, Japan
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24
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Martino S. Mechanobiology in Cells and Tissues. Int J Mol Sci 2023; 24:ijms24108564. [PMID: 37239910 DOI: 10.3390/ijms24108564] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2023] [Accepted: 05/09/2023] [Indexed: 05/28/2023] Open
Abstract
This Editorial is a comment on the success of the Special Issue "Mechanobiology in Cells and Tissues" published in the International Journal of Molecular Sciences [...].
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Affiliation(s)
- Sabata Martino
- Department of Chemistry, Biology and Biotechnologies, University of Perugia, Via del Giochetto, 06122 Perugia, Italy
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25
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Rabiei M, Joshi V, Fowlds K, Cho M, Bowling A. Long-term dynamic simulation of adipogenic differentiation of a human mesenchymal stem cell. MULTIBODY SYSTEM DYNAMICS 2023; 58:113-133. [PMID: 39995807 PMCID: PMC11848651 DOI: 10.1007/s11044-023-09888-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/05/2022] [Accepted: 02/07/2023] [Indexed: 02/26/2025]
Abstract
Multibody dynamic simulations of the mechanobiology of cellular processes have not been obtained for time histories of orders larger than one second even with the employment of supercomputers. A mechanobiologically representative model of a cellular process includes subcellular structures with small masses and lengths. A key development in this work is the inclusion of a coarse-grained representation of the cytoskeleton, based on the tensegrity model, with masses from femtogram to picogram in size and lengths from nanometers to microns in size. A second key development is the inclusion in the model of bodies that increase in mass over time. The forces acting on these bodies will be orders of magnitude larger than the masses. The correspondingly large accelerations necessitate the use of small time steps to obtain an accurate solution. Adipogenic differentiation, adipogenesis, of a human bone marrow-derived mesenchymal stem cell (hMSC) develops over a time span of two weeks in the experiment. Numerically integrating this multiscale model for such a long time period is computationally infeasible with conventional methods. A novel scaling approach based on the method of multiple scales is used herein to accurately simulate this two weeks of time history on a desktop computer in less than 3.5 hours. This much faster than real time simulation facilitates the study of the time dependent elements of adipogenesis and the mechanobiology of cellular processes in general.
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Affiliation(s)
- Manoochehr Rabiei
- Department of Mechanical and Aerospace Engineering, University of Texas at Arlington, Arlington, Texas 76019
| | - Vatsal Joshi
- Department of Mechanical and Aerospace Engineering, University of Texas at Arlington, Arlington, Texas 76019
| | - Kelli Fowlds
- Department of Bioengineering, University of Texas at Arlington, Arlington, Texas 76019
| | - Michael Cho
- Department of Bioengineering, University of Texas at Arlington, Arlington, Texas 76019
| | - Alan Bowling
- Department of Mechanical and Aerospace Engineering, University of Texas at Arlington, Arlington, Texas 76019
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26
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Mechanotransduction for Muscle Protein Synthesis via Mechanically Activated Ion Channels. Life (Basel) 2023; 13:life13020341. [PMID: 36836698 PMCID: PMC9962945 DOI: 10.3390/life13020341] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2023] [Revised: 01/24/2023] [Accepted: 01/26/2023] [Indexed: 02/03/2023] Open
Abstract
Cell mechanotransduction, the ability to detect physical forces and convert them into a series of biochemical events, is important for a wide range of physiological processes. Cells express an array of mechanosensors transducing physical forces into intracellular signaling cascades, including ion channels. Ion channels that can be directly activated by mechanical cues are known as mechanically activated (MA), or stretch-activated (SA), channels. In response to repeated exposures to mechanical stimulation in the form of resistance training, enhanced protein synthesis and fiber hypertrophy are elicited in skeletal muscle, whereas a lack of mechanical stimuli due to inactivity/mechanical unloading leads to reduced muscle protein synthesis and fiber atrophy. To date, the role of MA channels in the transduction of mechanical load to intracellular signaling pathways regulating muscle protein synthesis is poorly described. This review article will discuss MA channels in striated muscle, their regulation, and putative roles in the anabolic processes in muscle cells/fibers in response to mechanical stimuli.
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27
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Ma Q, Miri Z, Haugen HJ, Moghanian A, Loca D. Significance of mechanical loading in bone fracture healing, bone regeneration, and vascularization. J Tissue Eng 2023; 14:20417314231172573. [PMID: 37251734 PMCID: PMC10214107 DOI: 10.1177/20417314231172573] [Citation(s) in RCA: 54] [Impact Index Per Article: 27.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2023] [Accepted: 04/13/2023] [Indexed: 05/31/2023] Open
Abstract
In 1892, J.L. Wolff proposed that bone could respond to mechanical and biophysical stimuli as a dynamic organ. This theory presents a unique opportunity for investigations on bone and its potential to aid in tissue repair. Routine activities such as exercise or machinery application can exert mechanical loads on bone. Previous research has demonstrated that mechanical loading can affect the differentiation and development of mesenchymal tissue. However, the extent to which mechanical stimulation can help repair or generate bone tissue and the related mechanisms remain unclear. Four key cell types in bone tissue, including osteoblasts, osteoclasts, bone lining cells, and osteocytes, play critical roles in responding to mechanical stimuli, while other cell lineages such as myocytes, platelets, fibroblasts, endothelial cells, and chondrocytes also exhibit mechanosensitivity. Mechanical loading can regulate the biological functions of bone tissue through the mechanosensor of bone cells intraosseously, making it a potential target for fracture healing and bone regeneration. This review aims to clarify these issues and explain bone remodeling, structure dynamics, and mechano-transduction processes in response to mechanical loading. Loading of different magnitudes, frequencies, and types, such as dynamic versus static loads, are analyzed to determine the effects of mechanical stimulation on bone tissue structure and cellular function. Finally, the importance of vascularization in nutrient supply for bone healing and regeneration was further discussed.
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Affiliation(s)
- Qianli Ma
- Department of Biomaterials, Institute
of Clinical Dentistry, University of Oslo, Norway
- Department of Immunology, School of
Basic Medicine, Fourth Military Medical University, Xi’an, PR China
| | - Zahra Miri
- Department of Materials Engineering,
Isfahan University of Technology, Isfahan, Iran
| | - Håvard Jostein Haugen
- Department of Biomaterials, Institute
of Clinical Dentistry, University of Oslo, Norway
| | - Amirhossein Moghanian
- Department of Materials Engineering,
Imam Khomeini International University, Qazvin, Iran
| | - Dagnjia Loca
- Rudolfs Cimdins Riga Biomaterials
Innovations and Development Centre, Institute of General Chemical Engineering,
Faculty of Materials Science and Applied Chemistry, Riga Technical University, Riga,
Latvia
- Baltic Biomaterials Centre of
Excellence, Headquarters at Riga Technical University, Riga, Latvia
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28
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Rapid Downregulation of H3K4me3 Binding to Immunoregulatory Genes in Altered Gravity in Primary Human M1 Macrophages. Int J Mol Sci 2022; 24:ijms24010603. [PMID: 36614046 PMCID: PMC9820304 DOI: 10.3390/ijms24010603] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2022] [Revised: 12/26/2022] [Accepted: 12/28/2022] [Indexed: 12/31/2022] Open
Abstract
The sensitivity of human immune system cells to gravity changes has been investigated in numerous studies. Human macrophages mediate innate and thus rapid immune defense on the one hand and activate T- and B-cell-based adaptive immune response on the other hand. In this process they finally act as immunoeffector cells, and are essential for tissue regeneration and remodeling. Recently, we demonstrated in the human Jurkat T cell line that genes are differentially regulated in cluster structures under altered gravity. In order to study an in vivo near system of immunologically relevant human cells under physically real microgravity, we performed parabolic flight experiments with primary human M1 macrophages under highly standardized conditions and performed chromatin immunoprecipitation DNA sequencing (ChIP-Seq) for whole-genome epigenetic detection of the DNA-binding loci of the main transcription complex RNA polymerase II and the transcription-associated epigenetic chromatin modification H3K4me3. We identified an overall downregulation of H3K4me3 binding loci in altered gravity, which were unequally distributed inter- and intrachromosomally throughout the genome. Three-quarters of all affected loci were located on the p arm of the chromosomes chr5, chr6, chr9, and chr19. The genomic distribution of the downregulated H3K4me3 loci corresponds to a substantial extent to immunoregulatory genes. In microgravity, analysis of RNA polymerase II binding showed increased binding to multiple loci at coding sequences but decreased binding to central noncoding regions. Detection of altered DNA binding of RNA polymerase II provided direct evidence that gravity changes can lead to altered transcription. Based on this study, we hypothesize that the rapid transcriptional response to changing gravitational forces is specifically encoded in the epigenetic organization of chromatin.
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29
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Markov P, Zhu H, Boote C, Blain EJ. Delayed reorganisation of F-actin cytoskeleton and reversible chromatin condensation in scleral fibroblasts under simulated pathological strain. Biochem Biophys Rep 2022; 32:101338. [PMID: 36123992 PMCID: PMC9482111 DOI: 10.1016/j.bbrep.2022.101338] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2022] [Revised: 08/25/2022] [Accepted: 08/27/2022] [Indexed: 11/06/2022] Open
Abstract
Mechanical loading regulates the functional capabilities of the ocular system, particularly in the sclera (‘white of the eye’) – the principal load-bearing tissue of the ocular globe. Resident fibroblasts of the scleral eye wall are continuously subjected to fluctuating mechanical strains arising from eye movements, cerebrospinal fluid pressure and, most influentially, intra-ocular pressure (IOP). Whilst fibroblasts are hypothesised to actively participate in scleral biomechanics, to date limited information has been reported on how the macroscopic stresses and strains are transmitted via their cytoskeletal networks. In this study, the effect of applying either a ‘physiological load’ (simulating healthy IOP) or a ‘pathological load’ (simulating an elevated glaucomatous IOP) to bovine scleral fibroblasts, as a model of human glaucoma, was conducted to characterise cytoskeletal organisation, chromatin condensation and cell dimensions using immunofluorescence confocal microscopy. Quantification of cell parameters and cytoskeletal element anisotropy were subsequently performed using FibrilTool, and chromatin condensation parameter assessment through a bespoke MATLAB script. The novel findings suggest that physiological load-induced F-actin rearrangement is transient, whereas pathological load, recapitulating in vivo glaucomatous IOP levels, had a reversible and inhibitory influence on remodelling of the cytoskeletal architecture and, further, induction of chromatin condensation. Ultimately, this could compromise cell behaviour. These findings could provide valuable insight into the mechanism(s) used by scleral fibroblasts to mechanically adapt to support biomechanical tissue integrity, and how it could be potentially modified for therapeutic avenues targeting mechanically mediated ocular pathologies such as glaucoma.
Physiological strain induced a transient F-actin rearrangement in scleral fibroblasts. In contrast, pathological strain reversibly delayed F-actin rearrangement. Vimentin and β-tubulin networks were largely unaffected by strain regimens. Pathological strain reversibly increased chromatin condensation parameter. Pathological strain may induce ‘inhibition delay’ to confer cytoprotection.
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30
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Rubin J, van Wijnen AJ, Uzer G. Architectural control of mesenchymal stem cell phenotype through nuclear actin. Nucleus 2022; 13:35-48. [PMID: 35133922 PMCID: PMC8837231 DOI: 10.1080/19491034.2022.2029297] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2021] [Revised: 01/10/2022] [Accepted: 01/11/2022] [Indexed: 11/18/2022] Open
Abstract
There is growing appreciation that architectural components of the nucleus regulate gene accessibility by altering chromatin organization. While nuclear membrane connector proteins link the mechanosensitive actin cytoskeleton to the nucleoskeleton, actin's contribution to the inner architecture of the nucleus remains enigmatic. Control of actin transport into the nucleus, plus the presence of proteins that control actin structure (the actin tool-box) within the nucleus, suggests that nuclear actin may support biomechanical regulation of gene expression. Cellular actin structure is mechanoresponsive: actin cables generated through forces experienced at the plasma membrane transmit force into the nucleus. We posit that dynamic actin remodeling in response to such biomechanical cues provides a novel level of structural control over the epigenetic landscape. We here propose to bring awareness to the fact that mechanical forces can promote actin transfer into the nucleus and control structural arrangements as illustrated in mesenchymal stem cells, thereby modulating lineage commitment.
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Affiliation(s)
- Janet Rubin
- Department of Medicine, University of North Carolina, Chapel Hill, NC, USA
| | - Andre J. van Wijnen
- Department of Biochemistry, University of Vermont Medical School, Burlington, Vt, USA
| | - Gunes Uzer
- Department of Mechanical & Biomedical Engineering, Boise State University, Boise, ID, USA
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31
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Thiel CS, Vahlensieck C, Ullrich O. Assoziation schneller Reaktionen der Genexpression mit Änderungen der 3D-Chromatinkonformation in veränderter Schwerkraft. FLUGMEDIZIN · TROPENMEDIZIN · REISEMEDIZIN - FTR 2022. [DOI: 10.1055/a-1928-0420] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
ZUSAMMENFASSUNGDie molekularen Prinzipien bei der Transduktion von Schwerkraftänderungen in zelluläre Antwort- und Anpassungsprozesse sind bisher weitgehend unbekannt. Wir konnten in humanen Jurkat-T-Zellen zeigen, dass Gene bei veränderter Schwerkraft in Clusterstrukturen („gravity-responsive chromosomal regions“, GRCRs) differenziell reguliert werden. Durch Kombination mit Hochdurchsatz-Chromatin-Konformationsanalysen (Hi-C) konnte eine hochsignifikante Assoziation von GRCRs mit strukturellen 3D-Chromatinveränderungen identifiziert werden, die vor allem auf den kleinen Chromosomen (chr16–chr22) kolokalisieren. Wir fanden weiterhin Hinweise auf einen mechanistischen Zusammenhang zwischen Spleißprozessen und differenzieller Genexpression bei veränderter Schwerkraft. Somit haben wir erste Belege dafür gefunden, dass Änderungen der Schwerkraft in den Zellkern übertragen werden und dort 3D-Chromosomen-Konformationsänderungen hervorrufen, die mit einer schnellen Transkriptionsantwort verbunden sind. Wir vermuten, dass die schnelle genomische Antwort auf veränderte Gravitationskräfte in der Organisation des Chromatins spezifisch codiert ist.
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Affiliation(s)
- Cora S. Thiel
- Innovation Cluster Space and Aviation (UZH Space Hub), Universität Zürich, Schweiz
- Anatomisches Institut, Universität Zürich, Schweiz
- Raumfahrtmedizin, Fachbereich Wirtschaftsingenieurwesen, Ernst-Abbe-Hochschule Jena
- Weltraumbiotechnologie, Fakultät für Maschinenbau, Otto-von-Guericke-Universität Magdeburg
| | - Christian Vahlensieck
- Innovation Cluster Space and Aviation (UZH Space Hub), Universität Zürich, Schweiz
- Anatomisches Institut, Universität Zürich, Schweiz
| | - Oliver Ullrich
- Innovation Cluster Space and Aviation (UZH Space Hub), Universität Zürich, Schweiz
- Anatomisches Institut, Universität Zürich, Schweiz
- Raumfahrtmedizin, Fachbereich Wirtschaftsingenieurwesen, Ernst-Abbe-Hochschule Jena
- Weltraumbiotechnologie, Fakultät für Maschinenbau, Otto-von-Guericke-Universität Magdeburg
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Katsuta E, Takabe K, Vujcic M, Gottlieb PA, Dai T, Mercado-Perez A, Beyder A, Wang Q, Opyrchal M. Mechano-Sensing Channel PIEZO2 Enhances Invasive Phenotype in Triple-Negative Breast Cancer. Int J Mol Sci 2022; 23:9909. [PMID: 36077309 PMCID: PMC9455988 DOI: 10.3390/ijms23179909] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2022] [Revised: 08/25/2022] [Accepted: 08/27/2022] [Indexed: 11/20/2022] Open
Abstract
BACKGROUND Mechanically gated PIEZO channels lead to an influx of cations, activation of additional Ca2+ channels, and cell depolarization. This study aimed to investigate PIEZO2's role in breast cancer. METHODS The clinical relevance of PIEZO2 expression in breast cancer patient was analyzed in a publicly available dataset. Utilizing PIEZO2 overexpressed breast cancer cells, and in vitro and in vivo experiments were conducted. RESULTS High expression of PIEZO2 was correlated with a worse survival in triple-negative breast cancer (TNBC) but not in other subtypes. Increased PEIZO2 channel function was confirmed in PIEZO2 overexpressed cells after mechanical stimulation. PIEZO2 overexpressed cells showed increased motility and invasive phenotypes as well as higher expression of SNAIL and Vimentin and lower expression of E-cadherin in TNBC cells. Correspondingly, high expression of PIEZO2 was correlated with the increased expression of epithelial-mesenchymal transition (EMT)-related genes in a TNBC patient. Activated Akt signaling was observed in PIEZO2 overexpressed TNBC cells. PIEZO2 overexpressed MDA-MB-231 cells formed a significantly higher number of lung metastases after orthotopic implantation. CONCLUSION PIEZO2 activation led to enhanced SNAIL stabilization through Akt activation. It enhanced Vimentin and repressed E-cadherin transcription, resulting in increased metastatic potential and poor clinical outcomes in TNBC patients.
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Affiliation(s)
- Eriko Katsuta
- Department of Surgical Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA
| | - Kazuaki Takabe
- Department of Surgical Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA
- Department of Surgery, University at Buffalo Jacobs School of Medicine and Biomedical Sciences, The State University of New York, Buffalo, NY 14203, USA
- Department of Breast Surgery and Oncology, Tokyo Medical University, Tokyo 160-8402, Japan
- Department of Surgery, Yokohama City University, Yokohama 236-0004, Japan
- Department of Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan
- Department of Breast Surgery, Fukushima Medical University, Fukushima 960-1295, Japan
| | - Marija Vujcic
- Department of Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA
| | - Philip A. Gottlieb
- Physiology and Biophysics, State University of New York at Buffalo, Buffalo, NY 14203, USA
| | - Tao Dai
- Department of Cell Stress Biology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA
| | - Arnaldo Mercado-Perez
- Enteric Neuroscience Program, Division of Gastroenterology & Hepatology, Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN 55905, USA
| | - Arthur Beyder
- Enteric Neuroscience Program, Division of Gastroenterology & Hepatology, Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN 55905, USA
| | - Qingfei Wang
- Department of Medicine, Division of Hematology/Oncology, Indiana University School of Medicine, Indianapolis, IN 46202, USA
| | - Mateusz Opyrchal
- Department of Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA
- Department of Medicine, Division of Hematology/Oncology, Indiana University School of Medicine, Indianapolis, IN 46202, USA
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Germain P, Delalande A, Pichon C. Role of Muscle LIM Protein in Mechanotransduction Process. Int J Mol Sci 2022; 23:ijms23179785. [PMID: 36077180 PMCID: PMC9456170 DOI: 10.3390/ijms23179785] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2022] [Revised: 08/14/2022] [Accepted: 08/26/2022] [Indexed: 11/25/2022] Open
Abstract
The induction of protein synthesis is crucial to counteract the deconditioning of neuromuscular system and its atrophy. In the past, hormones and cytokines acting as growth factors involved in the intracellular events of these processes have been identified, while the implications of signaling pathways associated with the anabolism/catabolism ratio in reference to the molecular mechanism of skeletal muscle hypertrophy have been recently identified. Among them, the mechanotransduction resulting from a mechanical stress applied to the cell appears increasingly interesting as a potential pathway for therapeutic intervention. At present, there is an open question regarding the type of stress to apply in order to induce anabolic events or the type of mechanical strain with respect to the possible mechanosensing and mechanotransduction processes involved in muscle cells protein synthesis. This review is focused on the muscle LIM protein (MLP), a structural and mechanosensing protein with a LIM domain, which is expressed in the sarcomere and costamere of striated muscle cells. It acts as a transcriptional cofactor during cell proliferation after its nuclear translocation during the anabolic process of differentiation and rebuilding. Moreover, we discuss the possible opportunity of stimulating this mechanotransduction process to counteract the muscle atrophy induced by anabolic versus catabolic disorders coming from the environment, aging or myopathies.
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Affiliation(s)
- Philippe Germain
- UFR Sciences and Techniques, University of Orleans, 45067 Orleans, France
- Center for Molecular Biophysics, CNRS Orleans, 45071 Orleans, France
| | - Anthony Delalande
- UFR Sciences and Techniques, University of Orleans, 45067 Orleans, France
- Center for Molecular Biophysics, CNRS Orleans, 45071 Orleans, France
| | - Chantal Pichon
- UFR Sciences and Techniques, University of Orleans, 45067 Orleans, France
- Center for Molecular Biophysics, CNRS Orleans, 45071 Orleans, France
- Institut Universitaire de France, 1 Rue Descartes, 75231 Paris, France
- Correspondence:
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Role of Inflammasomes in Keloids and Hypertrophic Scars-Lessons Learned from Chronic Diabetic Wounds and Skin Fibrosis. Int J Mol Sci 2022; 23:ijms23126820. [PMID: 35743263 PMCID: PMC9223684 DOI: 10.3390/ijms23126820] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2022] [Revised: 06/13/2022] [Accepted: 06/14/2022] [Indexed: 02/06/2023] Open
Abstract
Keloids and hypertrophic scars are pathological cutaneous scars. They arise from excessive wound healing, which induces chronic dermal inflammation and results in overwhelming fibroblast production of extracellular matrix. Their etiology is unclear. Inflammasomes are multiprotein complexes that are important in proinflammatory innate-immune system responses. We asked whether inflammasomes participate in pathological scarring by examining the literature on scarring, diabetic wounds (also characterized by chronic inflammation), and systemic sclerosis (also marked by fibrosis). Pathological scars are predominantly populated by anti-inflammatory M2 macrophages and recent literature hints that this could be driven by non-canonical inflammasome signaling. Diabetic-wound healing associates with inflammasome activation in immune (macrophages) and non-immune (keratinocytes) cells. Fibrotic conditions associate with inflammasome activation and inflammasome-induced transition of epithelial cells/endothelial cells/macrophages into myofibroblasts that deposit excessive extracellular matrix. Studies suggest that mechanical stimuli activate inflammasomes via the cytoskeleton and that mechanotransduction-inflammasome crosstalk is involved in fibrosis. Further research should examine (i) the roles that various inflammasome types in macrophages, (myo)fibroblasts, and other cell types play in keloid development and (ii) how mechanical stimuli interact with inflammasomes and thereby drive scar growth. Such research is likely to significantly advance our understanding of pathological scarring and aid the development of new therapeutic strategies.
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Ravasio A, Morselli E, Bertocchi C. Mechanoautophagy: Synergies Between Autophagy and Cell Mechanotransduction at Adhesive Complexes. Front Cell Dev Biol 2022; 10:917662. [PMID: 35721483 PMCID: PMC9198486 DOI: 10.3389/fcell.2022.917662] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2022] [Accepted: 05/13/2022] [Indexed: 12/15/2022] Open
Abstract
Cells are exposed and respond to various mechanical forces and physical cues stemming from their environment. This interaction has been seen to differentially regulate various cellular processes for maintenance of homeostasis, of which autophagy represents one of the major players. In addition, autophagy has been suggested to regulate mechanical functions of the cells including their interaction with the environment. In this minireview, we summarize the state of the art of the fascinating interplay between autophagy and the mechanotransduction machinery associated with cell adhesions, that we name ¨Mechanoautophagy¨
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Affiliation(s)
- Andrea Ravasio
- Institute for Biological and Medical Engineering Schools of Engineering, Medicine and Biological Sciences, Pontificia Universidad Católica de Chile, Santiago, Chile
- *Correspondence: Cristina Bertocchi, ; Andrea Ravasio,
| | - Eugenia Morselli
- Department of Basic Sciences, Faculty of Medicine and Sciences, Universidad San Sebastián, Santiago, Chile
| | - Cristina Bertocchi
- Laboratory for Molecular Mechanics of Cell Adhesion, Department of Physiology Pontificia Universidad Católica de Chile, Santiago, Chile
- *Correspondence: Cristina Bertocchi, ; Andrea Ravasio,
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Kohl P, Greiner J, Rog-Zielinska EA. Electron microscopy of cardiac 3D nanodynamics: form, function, future. Nat Rev Cardiol 2022; 19:607-619. [PMID: 35396547 DOI: 10.1038/s41569-022-00677-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 02/04/2022] [Indexed: 11/09/2022]
Abstract
The 3D nanostructure of the heart, its dynamic deformation during cycles of contraction and relaxation, and the effects of this deformation on cell function remain largely uncharted territory. Over the past decade, the first inroads have been made towards 3D reconstruction of heart cells, with a native resolution of around 1 nm3, and of individual molecules relevant to heart function at a near-atomic scale. These advances have provided access to a new generation of data and have driven the development of increasingly smart, artificial intelligence-based, deep-learning image-analysis algorithms. By high-pressure freezing of cardiomyocytes with millisecond accuracy after initiation of an action potential, pseudodynamic snapshots of contraction-induced deformation of intracellular organelles can now be captured. In combination with functional studies, such as fluorescence imaging, exciting insights into cardiac autoregulatory processes at nano-to-micro scales are starting to emerge. In this Review, we discuss the progress in this fascinating new field to highlight the fundamental scientific insight that has emerged, based on technological breakthroughs in biological sample preparation, 3D imaging and data analysis; to illustrate the potential clinical relevance of understanding 3D cardiac nanodynamics; and to predict further progress that we can reasonably expect to see over the next 10 years.
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Affiliation(s)
- Peter Kohl
- Institute for Experimental Cardiovascular Medicine, University Heart Center and Faculty of Medicine, University of Freiburg, Freiburg, Germany.,Faculty of Engineering, University of Freiburg, Freiburg, Germany.,Centre for Integrative Biological Signalling Studies (CIBSS), University of Freiburg, Freiburg, Germany
| | - Joachim Greiner
- Institute for Experimental Cardiovascular Medicine, University Heart Center and Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Eva A Rog-Zielinska
- Institute for Experimental Cardiovascular Medicine, University Heart Center and Faculty of Medicine, University of Freiburg, Freiburg, Germany.
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Kulkarni T, Mukhopadhyay D, Bhattacharya S. Dynamic alteration of poroelastic attributes as determinant membrane nanorheology for endocytosis of organ specific targeted gold nanoparticles. J Nanobiotechnology 2022; 20:74. [PMID: 35135558 PMCID: PMC8822666 DOI: 10.1186/s12951-022-01276-1] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2021] [Accepted: 01/20/2022] [Indexed: 01/21/2023] Open
Abstract
Background Efficacy of targeted drug delivery using nanoparticles relies on several factors including the uptake mechanisms such as phagocytosis, macropinocytosis, micropinocytosis and receptor mediated endocytosis. These mechanisms have been studied with respect to the alteration in signaling mechanisms, cellular morphology, and linear nanomechanical properties (NMPs). Commonly employed classical contact mechanics models to address cellular NMPs fail to address mesh like structure consisting of bilayer lipids and proteins of cell membrane. To overcome this technical challenge, we employed poroelastic model which accounts for the biphasic nature of cells including their porous behavior exhibiting both solid like (fluid storage) and liquid like (fluid dissipate) behavior. Results In this study, we employed atomic force microscopy to monitor the influence of surface engineering of gold nanoparticles (GNPs) to the alteration of nonlinear NMPs such as drained Poisson’s ratio, effective shear stress, diffusion constant and pore dimensions of cell membranes during their uptake. Herein, we used pancreatic cancer (PDAC) cell lines including Panc1, AsPC-1 and endothelial cell (HUVECs) to understand the receptor-dependent and -independent endocytosis of two different GNPs derived using plectin-1 targeting peptide (PTP-GNP) and corresponding scrambled peptide (sPEP-GNP). Compared to untreated cells, in case of receptor dependent endocytosis of PTP-GNPs diffusion coefficient altered ~ 1264-fold and ~ 1530-fold and pore size altered ~ 320-fold and ~ 260-fold in Panc1 and AsPC-1 cells, respectively. Whereas for receptor independent mechanisms, we observed modest alteration in diffusion coefficient and pore size, in these cells compared to untreated cells. Effective shear stress corresponding to 7.38 ± 0.15 kPa and 20.49 ± 0.39 kPa in PTP-GNP treatment in Panc1 and AsPC-1, respectively was significantly more than that for sPEP-GNP. These results demonstrate that with temporal recruitment of plectin-1 during receptor mediated endocytosis affects the poroelastic attributes of the membrane. Conclusion This study confirms that nonlinear NMPs of cell membrane are directly associated with the uptake mechanism of nanoparticles and can provide promising insights of the nature of endocytosis mechanism involved for organ specific drug delivery using nanoparticles. Hence, nanomechanical analysis of cell membrane using this noninvasive, label-free and live-cell analytical tool can therefore be instrumental to evaluate therapeutic benefit of nanoformulations. Graphical Abstract ![]()
Supplementary Information The online version contains supplementary material available at 10.1186/s12951-022-01276-1.
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Affiliation(s)
- Tanmay Kulkarni
- Department of Biochemistry and Molecular Biology, Mayo College of Medicine and Science, Griffin 413, Mayo Clinic Florida, 4500 San Pablo Road S, Jacksonville, FL, 32224, USA
| | - Debabrata Mukhopadhyay
- Department of Biochemistry and Molecular Biology, Mayo College of Medicine and Science, Griffin 413, Mayo Clinic Florida, 4500 San Pablo Road S, Jacksonville, FL, 32224, USA.,Department of Physiology and Biomedical Engineering, Mayo College of Medicine and Science, Jacksonville, FL, USA
| | - Santanu Bhattacharya
- Department of Biochemistry and Molecular Biology, Mayo College of Medicine and Science, Griffin 413, Mayo Clinic Florida, 4500 San Pablo Road S, Jacksonville, FL, 32224, USA. .,Department of Physiology and Biomedical Engineering, Mayo College of Medicine and Science, Jacksonville, FL, USA.
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Xiong Y, Yao J, Zheng Y, Shen F, Zhao H, Hu J, Leng B, Yang P, Liu X. Comprehensive mass spectrometry for development of proteomic biomarkers of intracranial aneurysms. Talanta 2021; 240:123159. [PMID: 34973552 DOI: 10.1016/j.talanta.2021.123159] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2021] [Revised: 12/13/2021] [Accepted: 12/19/2021] [Indexed: 10/19/2022]
Abstract
Protein biomarkers of intracranial aneurysm (IA) are essential for early detection and prediction of its rupture to facilitate the diagnosis and clinical management of the disease, monitor treatment response and detect recurrence. Here, we developed a comprehensive strategy for IA biomarker discovery by analyzing tissues from an animal model (n = 4) and serum from human patients (n = 60) using isobaric tandem mass tags-based quantitative proteomics. A total of 4811 and 562 proteins were identified from aneurysm tissue and serum samples, respectively. The 223 candidate protein biomarkers were further validated in an independent serum cohort (n = 30) by multiple reaction monitoring analysis. Combined with a logistic regression model, we built a diagnostic classifier P2 (FCN2 & RARRES2) to differentiate IA from healthy controls with accuracy of 93.3%, as well as a diagnostic classifier P7 (ADAM12, APOL3, F9, C3, CEACAM1, ICAM3, KLHDC7A) to classify ruptured IA from unruptured IA with accuracy of 95.0%. Taken together, our results suggest a valuable strategy for biomarker discovery and patient stratification in IA.
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Affiliation(s)
- Yueting Xiong
- The Fifth People's Hospital of Shanghai, Shanghai Key Laboratory of Medical Epigenetics, The International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China
| | - Jun Yao
- The Fifth People's Hospital of Shanghai, Shanghai Key Laboratory of Medical Epigenetics, The International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China
| | - Yongtao Zheng
- Department of Neurosurgery, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Fenglin Shen
- The Fifth People's Hospital of Shanghai, Shanghai Key Laboratory of Medical Epigenetics, The International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China
| | - Huanhuan Zhao
- The Fifth People's Hospital of Shanghai, Shanghai Key Laboratory of Medical Epigenetics, The International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China
| | - Jia Hu
- Huashan Hospital, Fudan University, Shanghai, 200032, China
| | - Bing Leng
- Huashan Hospital, Fudan University, Shanghai, 200032, China
| | - Pengyuan Yang
- The Fifth People's Hospital of Shanghai, Shanghai Key Laboratory of Medical Epigenetics, The International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China
| | - Xiaohui Liu
- The Fifth People's Hospital of Shanghai, Shanghai Key Laboratory of Medical Epigenetics, The International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China.
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Zhang H, Wang S, Lei C, Li G, Wang B. Experimental study of negative pressure wound therapy combined with platelet-rich fibrin for bone-exposed wounds. Regen Med 2021; 17:23-35. [PMID: 34905932 DOI: 10.2217/rme-2021-0043] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
Aim: To evaluate the efficacy of negative pressure wound therapy (NPWT) combined with platelet-rich fibrin (PRF) in treating bone-exposed wounds and explore its possible mechanism. Materials & methods: A bone-exposed wound was created in a total of 32 healthy Sprague-Dawley rats, which were divided into either control group, NPWT group, PRF group or both (N + P group). The bone-exposed area, skin contraction rate and granulation coverage and the level of growth factors in granulation tissue were determined on days 4, 7 and 10. Results: The N + P group showed significantly higher wound closure rate than that achieved with others respectively. Four factors were significantly higher in N + P group than in the other three groups. Conclusion: Combination of NPWT and PRF can repair bone-exposed wounds effectively and accelerate wound healing.
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Affiliation(s)
- Hong Zhang
- Department of Plastic & Cosmetic Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou Fujian, 350000, PR China.,Department of Pediatric Surgery, Fujian Children's Hospital, Fuzhou Fujian, 350000, PR China.,Fujian Branch of Shanghai Children's Medical Center Affiliated to Shanghai Jiaotong University School of Medicine, Fuzhou Fujian, 350000, PR China.,Fujian Maternity & Child Health Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou Fujian, 350000, PR China
| | - Songyu Wang
- Department of Plastic & Cosmetic Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou Fujian, 350000, PR China
| | - Chen Lei
- Department of Plastic & Cosmetic Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou Fujian, 350000, PR China
| | - Guanmin Li
- Department of Plastic & Cosmetic Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou Fujian, 350000, PR China
| | - Biao Wang
- Department of Plastic & Cosmetic Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou Fujian, 350000, PR China
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Gorelova V, Sprakel J, Weijers D. Plant cell polarity as the nexus of tissue mechanics and morphogenesis. NATURE PLANTS 2021; 7:1548-1559. [PMID: 34887521 DOI: 10.1038/s41477-021-01021-w] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/11/2021] [Accepted: 10/13/2021] [Indexed: 05/20/2023]
Abstract
How reproducible body patterns emerge from the collective activity of individual cells is a key question in developmental biology. Plant cells are encaged in their walls and unable to migrate. Morphogenesis thus relies on directional cell division, by precise positioning of division planes, and anisotropic cellular growth, mediated by regulated mechanical inhomogeneity of the walls. Both processes require the prior establishment of cell polarity, marked by the formation of polar domains at the plasma membrane, in a number of developmental contexts. The establishment of cell polarity involves biochemical cues, but increasing evidence suggests that mechanical forces also play a prominent instructive role. While evidence for mutual regulation between cell polarity and tissue mechanics is emerging, the nature of this bidirectional feedback remains unclear. Here we review the role of cell polarity at the interface of tissue mechanics and morphogenesis. We also aim to integrate biochemistry-centred insights with concepts derived from physics and physical chemistry. Lastly, we propose a set of questions that will help address the fundamental nature of cell polarization and its mechanistic basis.
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Affiliation(s)
- Vera Gorelova
- Laboratory of Biochemistry, Wageningen University and Research, Wageningen, the Netherlands
| | - Joris Sprakel
- Physical Chemistry and Soft Matter, Wageningen University and Research, Wageningen, the Netherlands
| | - Dolf Weijers
- Laboratory of Biochemistry, Wageningen University and Research, Wageningen, the Netherlands.
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Boghdady CM, Kalashnikov N, Mok S, McCaffrey L, Moraes C. Revisiting tissue tensegrity: Biomaterial-based approaches to measure forces across length scales. APL Bioeng 2021; 5:041501. [PMID: 34632250 PMCID: PMC8487350 DOI: 10.1063/5.0046093] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2021] [Accepted: 09/08/2021] [Indexed: 12/18/2022] Open
Abstract
Cell-generated forces play a foundational role in tissue dynamics and homeostasis and are critically important in several biological processes, including cell migration, wound healing, morphogenesis, and cancer metastasis. Quantifying such forces in vivo is technically challenging and requires novel strategies that capture mechanical information across molecular, cellular, and tissue length scales, while allowing these studies to be performed in physiologically realistic biological models. Advanced biomaterials can be designed to non-destructively measure these stresses in vitro, and here, we review mechanical characterizations and force-sensing biomaterial-based technologies to provide insight into the mechanical nature of tissue processes. We specifically and uniquely focus on the use of these techniques to identify characteristics of cell and tissue "tensegrity:" the hierarchical and modular interplay between tension and compression that provide biological tissues with remarkable mechanical properties and behaviors. Based on these observed patterns, we highlight and discuss the emerging role of tensegrity at multiple length scales in tissue dynamics from homeostasis, to morphogenesis, to pathological dysfunction.
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Affiliation(s)
| | - Nikita Kalashnikov
- Department of Chemical Engineering, McGill University, Montréal, Québec H3A 0C5, Canada
| | - Stephanie Mok
- Department of Chemical Engineering, McGill University, Montréal, Québec H3A 0C5, Canada
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Novak C, Ballinger MN, Ghadiali S. Mechanobiology of Pulmonary Diseases: A Review of Engineering Tools to Understand Lung Mechanotransduction. J Biomech Eng 2021; 143:110801. [PMID: 33973005 PMCID: PMC8299813 DOI: 10.1115/1.4051118] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2020] [Revised: 05/01/2021] [Indexed: 12/17/2022]
Abstract
Cells within the lung micro-environment are continuously subjected to dynamic mechanical stimuli which are converted into biochemical signaling events in a process known as mechanotransduction. In pulmonary diseases, the abrogated mechanical conditions modify the homeostatic signaling which influences cellular phenotype and disease progression. The use of in vitro models has significantly expanded our understanding of lung mechanotransduction mechanisms. However, our ability to match complex facets of the lung including three-dimensionality, multicellular interactions, and multiple simultaneous forces is limited and it has proven difficult to replicate and control these factors in vitro. The goal of this review is to (a) outline the anatomy of the pulmonary system and the mechanical stimuli that reside therein, (b) describe how disease impacts the mechanical micro-environment of the lung, and (c) summarize how existing in vitro models have contributed to our current understanding of pulmonary mechanotransduction. We also highlight critical needs in the pulmonary mechanotransduction field with an emphasis on next-generation devices that can simulate the complex mechanical and cellular environment of the lung. This review provides a comprehensive basis for understanding the current state of knowledge in pulmonary mechanotransduction and identifying the areas for future research.
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Affiliation(s)
- Caymen Novak
- Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Internal Medicine, The Davis Heart and Lung Research Institute, The Ohio State University, Wexner Medical Center, 473 West 12th Avenue, Columbus, OH 43210
| | - Megan N. Ballinger
- Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Internal Medicine, The Davis Heart and Lung Research Institute, The Ohio State University, Wexner Medical Center, 473 West 12th Avenue, Columbus, OH 43210
| | - Samir Ghadiali
- Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Internal Medicine, The Davis Heart and Lung Research Institute, The Ohio State University, Wexner Medical Center, 473 West 12th Avenue, Columbus, OH 43210; Department of Biomedical Engineering, The Ohio State University, 2124N Fontana Labs, 140 West 19th Avenue, Columbus, OH 43210
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Pulmonary arteries of Williams syndrome patients exhibit altered serotonin metabolism genes and degenerated medial layer architecture. Pediatr Res 2021; 90:1065-1072. [PMID: 33531674 DOI: 10.1038/s41390-020-01359-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/21/2020] [Revised: 12/16/2020] [Accepted: 12/18/2020] [Indexed: 11/08/2022]
Abstract
BACKGROUND Williams-Beuren syndrome (WS) is characterized by cardiovascular abnormalities associated with a multigene deletion on 7q11.23, in particular elastin (ELN). Peripheral pulmonary artery stenosis (PPAS) frequently affects pediatric patients with WS. Molecular investigation of WS pulmonary arterial (PA) tissue is limited by tissue scarcity. METHODS We compared transcriptomes, tissue architecture, and localized changes in protein expression in PA tissue from patients with WS (n = 8) and donors (n = 5). RESULTS Over 100 genes were differentially expressed at the ≥4-fold level, including genes related to the serotonin signaling pathway: >60-fold downregulation of serotonin transporter SLC6A4 and >3-fold upregulation of serotonin receptor HTR2A. Histologic examination revealed abnormal elastin distribution and smooth muscle cell morphology in WS PA, with markedly shorter, disorganized elastin fibers, and expanded proteoglycan-rich extracellular matrix between muscle layers. CONCLUSIONS There were significant abnormalities in the PA expression of genes regulating serotonin signaling, metabolism, and receptors in WS. Those changes were associated with distinct changes in the arterial structure and may play a role in the stenosis-promoting effects of elevated shear stress at PA bifurcations in WS. IMPACT Serotonin pathway signaling is significantly altered in the pulmonary arteries of patients with Williams syndrome and severe peripheral arterial stenosis. The present study compares the histological and biochemical characteristics of pulmonary arteries from patients with Williams syndrome to those of controls, something that has not, to our knowledge, been done previously. It demonstrates marked abnormalities in the pulmonary arteries of patients with Williams syndrome, especially significant pathologic alterations in the signaling of the serotonin pathway. The findings of this study provide direction for the development of potential therapies to treat pulmonary artery stenosis in patients with Williams syndrome.
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Swiatlowska P, Iskratsch T. Tools for studying and modulating (cardiac muscle) cell mechanics and mechanosensing across the scales. Biophys Rev 2021; 13:611-623. [PMID: 34765044 PMCID: PMC8553672 DOI: 10.1007/s12551-021-00837-2] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2021] [Accepted: 08/24/2021] [Indexed: 12/26/2022] Open
Abstract
Cardiomyocytes generate force for the contraction of the heart to pump blood into the lungs and body. At the same time, they are exquisitely tuned to the mechanical environment and react to e.g. changes in cell and extracellular matrix stiffness or altered stretching due to reduced ejection fraction in heart disease, by adapting their cytoskeleton, force generation and cell mechanics. Both mechanical sensing and cell mechanical adaptations are multiscale processes. Receptor interactions with the extracellular matrix at the nanoscale will lead to clustering of receptors and modification of the cytoskeleton. This in turn alters mechanosensing, force generation, cell and nuclear stiffness and viscoelasticity at the microscale. Further, this affects cell shape, orientation, maturation and tissue integration at the microscale to macroscale. A variety of tools have been developed and adapted to measure cardiomyocyte receptor-ligand interactions and forces or mechanics at the different ranges, resulting in a wealth of new information about cardiomyocyte mechanobiology. Here, we take stock at the different tools for exploring cardiomyocyte mechanosensing and cell mechanics at the different scales from the nanoscale to microscale and macroscale.
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Affiliation(s)
- Pamela Swiatlowska
- School of Engineering and Materials Science, Queen Mary University of London, London, UK
| | - Thomas Iskratsch
- School of Engineering and Materials Science, Queen Mary University of London, London, UK
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Gravitational Force-Induced 3D Chromosomal Conformational Changes Are Associated with Rapid Transcriptional Response in Human T Cells. Int J Mol Sci 2021; 22:ijms22179426. [PMID: 34502336 PMCID: PMC8430767 DOI: 10.3390/ijms22179426] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2021] [Revised: 08/26/2021] [Accepted: 08/27/2021] [Indexed: 12/14/2022] Open
Abstract
The mechanisms underlying gravity perception in mammalian cells are unknown. We have recently discovered that the transcriptome of cells in the immune system, which is the most affected system during a spaceflight, responds rapidly and broadly to altered gravity. To pinpoint potential underlying mechanisms, we compared gene expression and three-dimensional (3D) chromosomal conformational changes in human Jurkat T cells during the short-term gravitational changes in parabolic flight and suborbital ballistic rocket flight experiments. We found that differential gene expression in gravity-responsive chromosomal regions, but not differentially regulated single genes, are highly conserved between different real altered gravity comparisons. These coupled gene expression effects in chromosomal regions could be explained by underlying chromatin structures. Based on a high-throughput chromatin conformation capture (Hi-C) analysis in altered gravity, we found that small chromosomes (chr16–22, with the exception of chr18) showed increased intra- and interchromosomal interactions in altered gravity, whereby large chromosomes showed decreased interactions. Finally, we detected a nonrandom overlap between Hi-C-identified chromosomal interacting regions and gravity-responsive chromosomal regions (GRCRs). We therefore demonstrate the first evidence that gravitational force-induced 3D chromosomal conformational changes are associated with rapid transcriptional response in human T cells. We propose a general model of cellular sensitivity to gravitational forces, where gravitational forces acting on the cellular membrane are rapidly and mechanically transduced through the cytoskeleton into the nucleus, moving chromosome territories to new conformation states and their genes into more expressive or repressive environments, finally resulting in region-specific differential gene expression.
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Li Y, Zhan Q, Bao M, Yi J, Li Y. Biomechanical and biological responses of periodontium in orthodontic tooth movement: up-date in a new decade. Int J Oral Sci 2021; 13:20. [PMID: 34183652 PMCID: PMC8239047 DOI: 10.1038/s41368-021-00125-5] [Citation(s) in RCA: 144] [Impact Index Per Article: 36.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2020] [Revised: 04/29/2021] [Accepted: 04/30/2021] [Indexed: 02/05/2023] Open
Abstract
Nowadays, orthodontic treatment has become increasingly popular. However, the biological mechanisms of orthodontic tooth movement (OTM) have not been fully elucidated. We were aiming to summarize the evidences regarding the mechanisms of OTM. Firstly, we introduced the research models as a basis for further discussion of mechanisms. Secondly, we proposed a new hypothesis regarding the primary roles of periodontal ligament cells (PDLCs) and osteocytes involved in OTM mechanisms and summarized the biomechanical and biological responses of the periodontium in OTM through four steps, basically in OTM temporal sequences, as follows: (1) Extracellular mechanobiology of periodontium: biological, mechanical, and material changes of acellular components in periodontium under orthodontic forces were introduced. (2) Cell strain: the sensing, transduction, and regulation of mechanical stimuli in PDLCs and osteocytes. (3) Cell activation and differentiation: the activation and differentiation mechanisms of osteoblast and osteoclast, the force-induced sterile inflammation, and the communication networks consisting of sensors and effectors. (4) Tissue remodeling: the remodeling of bone and periodontal ligament (PDL) in the compression side and tension side responding to mechanical stimuli and root resorption. Lastly, we talked about the clinical implications of the updated OTM mechanisms, regarding optimal orthodontic force (OOF), acceleration of OTM, and prevention of root resorption.
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Affiliation(s)
- Yuan Li
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Qi Zhan
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Minyue Bao
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Jianru Yi
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
| | - Yu Li
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
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Melrose J, Hayes AJ, Bix G. The CNS/PNS Extracellular Matrix Provides Instructive Guidance Cues to Neural Cells and Neuroregulatory Proteins in Neural Development and Repair. Int J Mol Sci 2021; 22:5583. [PMID: 34070424 PMCID: PMC8197505 DOI: 10.3390/ijms22115583] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2021] [Revised: 05/11/2021] [Accepted: 05/17/2021] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND The extracellular matrix of the PNS/CNS is unusual in that it is dominated by glycosaminoglycans, especially hyaluronan, whose space filling and hydrating properties make essential contributions to the functional properties of this tissue. Hyaluronan has a relatively simple structure but its space-filling properties ensure micro-compartments are maintained in the brain ultrastructure, ensuring ionic niches and gradients are maintained for optimal cellular function. Hyaluronan has cell-instructive, anti-inflammatory properties and forms macro-molecular aggregates with the lectican CS-proteoglycans, forming dense protective perineuronal net structures that provide neural and synaptic plasticity and support cognitive learning. AIMS To highlight the central nervous system/peripheral nervous system (CNS/PNS) and its diverse extracellular and cell-associated proteoglycans that have cell-instructive properties regulating neural repair processes and functional recovery through interactions with cell adhesive molecules, receptors and neuroregulatory proteins. Despite a general lack of stabilising fibrillar collagenous and elastic structures in the CNS/PNS, a sophisticated dynamic extracellular matrix is nevertheless important in tissue form and function. CONCLUSIONS This review provides examples of the sophistication of the CNS/PNS extracellular matrix, showing how it maintains homeostasis and regulates neural repair and regeneration.
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Affiliation(s)
- James Melrose
- Raymond Purves Bone and Joint Research Laboratory, Kolling Institute, Northern Sydney Local Health District, St. Leonards, NSW 2065, Australia
- Graduate School of Biomedical Engineering, University of New South Wales, Sydney, NSW 2052, Australia
- Sydney Medical School, Northern, The University of Sydney, Sydney, NSW 2052, Australia
- Faculty of Medicine and Health, The University of Sydney, Royal North Shore Hospital, St. Leonards, NSW 2065, Australia
| | - Anthony J. Hayes
- Bioimaging Research Hub, Cardiff School of Biosciences, Cardiff University, Cardiff CF10 3AX, UK;
| | - Gregory Bix
- Clinical Neuroscience Research Center, Departments of Neurosurgery and Neurology, Tulane University School of Medicine, New Orleans, LA 70112, USA;
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Chen Z, Zhou T, Hu J, Duan H. Quartz Crystal Microbalance with Dissipation Monitoring of Dynamic Viscoelastic Changes of Tobacco BY-2 Cells under Different Osmotic Conditions. BIOSENSORS 2021; 11:136. [PMID: 33925584 PMCID: PMC8145959 DOI: 10.3390/bios11050136] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/17/2021] [Revised: 04/21/2021] [Accepted: 04/22/2021] [Indexed: 01/03/2023]
Abstract
The plant cell mechanics, including turgor pressure and wall mechanical properties, not only determine the growth of plant cells, but also reflect the functional and structural changes of plant cells under biotic and abiotic stresses. However, there are currently no appropriate techniques allowing to monitor the complex mechanical properties of living plant cells non-invasively and continuously. In this work, quartz crystal microbalance with dissipation (QCM-D) monitoring technique with overtones (3-9) was used for the dynamic monitoring of adhesions of living tobacco BY-2 cells onto positively charged N,N-dimethyl-N-propenyl-2-propen-1-aminiumchloride homopolymer (PDADMAC)/SiO2 QCM crystals under different concentrations of mannitol (CM) and the subsequent effects of osmotic stresses. The cell viscoelastic index (CVIn) (CVIn = ΔD⋅n/ΔF) was used to characterize the viscoelastic properties of BY-2 cells under different osmotic conditions. Our results indicated that lower overtones of QCM could detect both the cell wall and cytoskeleton structures allowing the detection of plasmolysis phenomena; whereas higher overtones could only detect the cell wall's mechanical properties. The QCM results were further discussed with the morphological changes of the BY-2 cells by an optical microscopy. The dynamic changes of cell's generated forces or cellular structures of plant cells caused by external stimuli (or stresses) can be traced by non-destructive and dynamic monitoring of cells' viscoelasticity, which provides a new way for the characterization and study of plant cells. QCM-D could map viscoelastic properties of different cellular structures in living cells and could be used as a new tool to test the mechanical properties of plant cells.
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Affiliation(s)
- Zongxing Chen
- College of Bioscience and Biotechnology, Hunan Agricultural University, Changsha 410128, China; (Z.C.); (J.H.); (H.D.)
- Hunan Provincial Engineering Technology Research Center for Cell Mechanics and Function Analysis, Changsha 410128, China
| | - Tiean Zhou
- College of Bioscience and Biotechnology, Hunan Agricultural University, Changsha 410128, China; (Z.C.); (J.H.); (H.D.)
- Hunan Provincial Engineering Technology Research Center for Cell Mechanics and Function Analysis, Changsha 410128, China
| | - Jiajin Hu
- College of Bioscience and Biotechnology, Hunan Agricultural University, Changsha 410128, China; (Z.C.); (J.H.); (H.D.)
- Hunan Provincial Engineering Technology Research Center for Cell Mechanics and Function Analysis, Changsha 410128, China
| | - Haifeng Duan
- College of Bioscience and Biotechnology, Hunan Agricultural University, Changsha 410128, China; (Z.C.); (J.H.); (H.D.)
- Hunan Provincial Engineering Technology Research Center for Cell Mechanics and Function Analysis, Changsha 410128, China
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What Are the Potential Roles of Nuclear Perlecan and Other Heparan Sulphate Proteoglycans in the Normal and Malignant Phenotype. Int J Mol Sci 2021; 22:ijms22094415. [PMID: 33922532 PMCID: PMC8122901 DOI: 10.3390/ijms22094415] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2021] [Revised: 04/19/2021] [Accepted: 04/19/2021] [Indexed: 12/27/2022] Open
Abstract
The recent discovery of nuclear and perinuclear perlecan in annulus fibrosus and nucleus pulposus cells and its known matrix stabilizing properties in tissues introduces the possibility that perlecan may also have intracellular stabilizing or regulatory roles through interactions with nuclear envelope or cytoskeletal proteins or roles in nucleosomal-chromatin organization that may regulate transcriptional factors and modulate gene expression. The nucleus is a mechano-sensor organelle, and sophisticated dynamic mechanoresponsive cytoskeletal and nuclear envelope components support and protect the nucleus, allowing it to perceive and respond to mechano-stimulation. This review speculates on the potential roles of perlecan in the nucleus based on what is already known about nuclear heparan sulphate proteoglycans. Perlecan is frequently found in the nuclei of tumour cells; however, its specific role in these diseased tissues is largely unknown. The aim of this review is to highlight probable roles for this intriguing interactive regulatory proteoglycan in the nucleus of normal and malignant cell types.
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Giannopoulos A, Svensson RB, Yeung CYC, Kjaer M, Magnusson SP. Effects of genipin crosslinking on mechanical cell-matrix interaction in 3D engineered tendon constructs. J Mech Behav Biomed Mater 2021; 119:104508. [PMID: 33857874 DOI: 10.1016/j.jmbbm.2021.104508] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2020] [Revised: 03/31/2021] [Accepted: 04/01/2021] [Indexed: 11/18/2022]
Abstract
It is well known that cells can generate endogenous forces onto the extracellular matrix, but to what extent the mechanical properties of the matrix influences these endogenous cellular forces remains unclear. We therefore sought to quantify the influence of matrix rigidity on cell-matrix interactions by inducing cross-links using increasing concentrations of genipin (0.01-1 mM) or by blocking cross-link formation using beta-aminopropionitrile (BAPN) in engineered human tendon tissue constructs. The cell-matrix mechanics of the tendon constructs were evaluated as cell-generated tissue re-tensioning and stress-relaxation responses using a novel custom-made force monitor, which can apply and detect tensional forces in real-time in addition to mechanical failure testing. Genipin treatment had no influence on the biochemical profile (hydroxyproline, glycosaminoglycan and DNA content) of the constructs and cell viability was comparable between genipin-treated and control constructs, except at the highest genipin concentration. Endogenous re-tension after unloading was significantly decreased with increasing genipin concentrations compared to controls. Mechanical failure testing of tendon constructs showed increased (56%) peak stress at the highest genipin concentration but decreased (72%) with BAPN treatment when compared to controls. Tendon construct stiffness increased with high genipin concentrations (0.1 and 1 mM) and decreased by 70% in BAPN-treated constructs, relative to the controls. These data demonstrate that human tendon fibroblasts regulate their force exertion inversely proportional to increased cross-link capacity but did so independently of matrix stiffness. Overall, these findings support the notion of an interaction between cell force generation and cross-linking, and thus a role for this interplay in mechanical homeostasis of the tissue.
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Affiliation(s)
- A Giannopoulos
- Institute of Sports Medicine Copenhagen, Department of Orthopedic Surgery, Bispebjerg-Frederiksberg Hospital and Center for Healthy Aging, Faculty of Health Sciences, University of Copenhagen, Denmark.
| | - R B Svensson
- Institute of Sports Medicine Copenhagen, Department of Orthopedic Surgery, Bispebjerg-Frederiksberg Hospital and Center for Healthy Aging, Faculty of Health Sciences, University of Copenhagen, Denmark
| | - C Y C Yeung
- Institute of Sports Medicine Copenhagen, Department of Orthopedic Surgery, Bispebjerg-Frederiksberg Hospital and Center for Healthy Aging, Faculty of Health Sciences, University of Copenhagen, Denmark
| | - M Kjaer
- Institute of Sports Medicine Copenhagen, Department of Orthopedic Surgery, Bispebjerg-Frederiksberg Hospital and Center for Healthy Aging, Faculty of Health Sciences, University of Copenhagen, Denmark
| | - S P Magnusson
- Institute of Sports Medicine Copenhagen, Department of Orthopedic Surgery, Bispebjerg-Frederiksberg Hospital and Center for Healthy Aging, Faculty of Health Sciences, University of Copenhagen, Denmark; Department of Physical and Occupational Therapy, Bispebjerg-Frederiksberg Hospital, Copenhagen, Denmark
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