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Valenti D, Atlante A. Sound Matrix Shaping of Living Matter: From Macrosystems to Cell Microenvironment, Where Mitochondria Act as Energy Portals in Detecting and Processing Sound Vibrations. Int J Mol Sci 2024; 25:6841. [PMID: 38999952 PMCID: PMC11241420 DOI: 10.3390/ijms25136841] [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: 05/06/2024] [Revised: 06/18/2024] [Accepted: 06/19/2024] [Indexed: 07/14/2024] Open
Abstract
Vibration and sound are the shaping matrix of the entire universe. Everything in nature is shaped by energy vibrating and communicating through its own sound trail. Every cell within our body vibrates at defined frequencies, generating its peculiar "sound signature". Mitochondria are dynamic, energy-transforming, biosynthetic, and signaling organelles that actively transduce biological information. Novel research has shown that the mitochondrial function of mammalian cells can be modulated by various energetic stimuli, including sound vibrations. Regarding acoustic vibrations, definite types of music have been reported to produce beneficial impacts on human health. In very recent studies, the effects of different sound stimuli and musical styles on cellular function and mitochondrial activity were evaluated and compared in human cells cultured in vitro, investigating the underlying responsible molecular mechanisms. This narrative review will take a multilevel trip from macro to intracellular microenvironment, discussing the intimate vibrational sound activities shaping living matter, delving deeper into the molecular mechanisms underlying the sound modulation of biological systems, and mainly focusing our discussion on novel evidence showing the competence of mitochondria in acting as energy portals capable of sensing and transducing the subtle informational biofields of sound vibration.
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Affiliation(s)
- Daniela Valenti
- Institute of Biomembranes, Bioenergetics and Molecular Biotechnologies (IBIOM), National Research Council (CNR), Via G. Amendola 122/O, 70126 Bari, Italy
| | - Anna Atlante
- Institute of Biomembranes, Bioenergetics and Molecular Biotechnologies (IBIOM), National Research Council (CNR), Via G. Amendola 122/O, 70126 Bari, Italy
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Capareli F, Costa F, Tuszynski JA, Sousa MC, Setogute YDC, Lima PD, Carvalho L, Santos E, Gumz BP, Sabbaga J, de Castria TB, Jardim DL, Freitas D, Horvat N, Bezerra ROF, Testagrossa L, Costa T, Zanesco T, Iemma AF, Abou‐Alfa GK. Low-energy amplitude-modulated electromagnetic field exposure: Feasibility study in patients with hepatocellular carcinoma. Cancer Med 2023; 12:12402-12412. [PMID: 37184216 PMCID: PMC10278519 DOI: 10.1002/cam4.5944] [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: 11/29/2022] [Revised: 03/23/2023] [Accepted: 03/31/2023] [Indexed: 05/16/2023] Open
Abstract
BACKGROUND Patients with advanced hepatocellular carcinoma (HCC) and poor liver function lack effective systemic therapies. Low-energy electromagnetic fields (EMFs) can influence cell biological processes via non-thermal effects and may represent a new treatment option. METHODS This single-site feasibility trial enrolled patients with advanced HCC, Child-Pugh A and B, Eastern Cooperative Oncology Group 0-2. Patients underwent 90-min amplitude-modulated EMF exposure procedures every 2-4 weeks, using the AutEMdev (Autem Therapeutics). Patients could also receive standard care. The primary endpoints were safety and the identification of hemodynamic variability patterns. Exploratory endpoints included health-related quality of life (HRQoL), overall survival (OS). and objective response rate (ORR) using RECIST v1.1. RESULTS Sixty-six patients with advanced HCC received 539 AutEMdev procedures (median follow-up, 30 months). No serious adverse events occurred during procedures. Self-limiting grade 1 somnolence occurred in 78.7% of patients. Hemodynamic variability during EMF exposure was associated with specific amplitude-modulation frequencies. HRQoL was maintained or improved among patients remaining on treatment. Median OS was 11.3 months (95% confidence interval [CI]: 6.0, 16.6) overall (16.0 months [95% CI: 4.4, 27.6] and 12.0 months [6.4, 17.6] for combination therapy and monotherapy, respectively). ORR was 24.3% (32% and 17% for combination therapy and monotherapy, respectively). CONCLUSION AutEMdev EMF exposure has an excellent safety profile in patients with advanced HCC. Hemodynamic alterations at personalized frequencies may represent a surrogate of anti-tumor efficacy. NCT01686412.
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Affiliation(s)
| | - Frederico Costa
- Oncology DepartmentHospital Sírio‐LibanêsSão PauloBrazil
- Autem Medical LLCHanoverNew HampshireUSA
| | - Jack A. Tuszynski
- Autem Medical LLCHanoverNew HampshireUSA
- Division of Experimental Oncology, Department of OncologyCross Cancer Institute, University of AlbertaEdmontonAlbertaCanada
| | | | | | - Pablo D. Lima
- Oncology DepartmentHospital Sírio‐LibanêsSão PauloBrazil
| | | | - Elizabeth Santos
- Oncology DepartmentHospital Sírio‐LibanêsSão PauloBrazil
- Oncology DepartmentA. C. Camargo Cancer CenterSão PauloBrazil
| | - Brenda P. Gumz
- Oncology DepartmentHospital Sírio‐LibanêsSão PauloBrazil
| | - Jorge Sabbaga
- Oncology DepartmentHospital Sírio‐LibanêsSão PauloBrazil
| | | | | | | | - Natally Horvat
- Memorial Sloan Kettering Cancer CenterNew YorkNew YorkUSA
| | | | | | - Tiago Costa
- Santa Casa de São Paulo School of Medical SciencesSão PauloBrazil
| | | | - Antonio F. Iemma
- Institute of Mathematics and Statistics, University of São PauloSão PauloBrazil
| | - Ghassan K. Abou‐Alfa
- Memorial Sloan Kettering Cancer CenterNew YorkNew YorkUSA
- Weill Medical College at Cornell UniversityNew YorkNew YorkUSA
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Dal Lin C, Radu CM, Vitiello G, Romano P, Polcari A, Iliceto S, Simioni P, Tona F. Sounds Stimulation on In Vitro HL1 Cells: A Pilot Study and a Theoretical Physical Model. Int J Mol Sci 2020; 22:ijms22010156. [PMID: 33375749 PMCID: PMC7796405 DOI: 10.3390/ijms22010156] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2020] [Revised: 12/19/2020] [Accepted: 12/20/2020] [Indexed: 02/07/2023] Open
Abstract
Mechanical vibrations seem to affect the behaviour of different cell types and the functions of different organs. Pressure waves, including acoustic waves (sounds), could affect cytoskeletal molecules via coherent changes in their spatial organization and mechano-transduction signalling. We analyzed the sounds spectra and their fractal features. Cardiac muscle HL1 cells were exposed to different sounds, were stained for cytoskeletal markers (phalloidin, beta-actin, alpha-tubulin, alpha-actinin-1), and studied with multifractal analysis (using FracLac for ImageJ). A single cell was live-imaged and its dynamic contractility changes in response to each different sound were analysed (using Musclemotion for ImageJ). Different sound stimuli seem to influence the contractility and the spatial organization of HL1 cells, resulting in a different localization and fluorescence emission of cytoskeletal proteins. Since the cellular behaviour seems to correlate with the fractal structure of the sound used, we speculate that it can influence the cells by virtue of the different sound waves’ geometric properties that we have photographed and filmed. A theoretical physical model is proposed to explain our results, based on the coherent molecular dynamics. We stress the role of the systemic view in the understanding of the biological activity.
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Affiliation(s)
- Carlo Dal Lin
- Department of Cardiac, Thoracic and Vascular Sciences, Padua University Medical School, 35100 Padua, Italy; (S.I.); (F.T.)
- Correspondence: ; Tel.: +39-049-8218642; Fax: +39-049-8211802
| | - Claudia Maria Radu
- Department of Women’s and Children’s Health, University of Padua, 35100 Padua, Italy;
- Department of Medicine, Thrombotic and Haemorrhagic Diseases Unit, Veneto Region Haemophilia and Thrombophilia Centre, University of Padua Medical School, 35100 Padua, Italy;
| | - Giuseppe Vitiello
- Department of Physics “E.R. Caianiello”, Salerno University, Fisciano, 84084 Salerno, Italy;
| | - Paola Romano
- Department of Sciences and Technologies, Sannio University, 82100 Benevento, Italy;
- CNR-SPIN Salerno, Baronissi, 84084 Salerno, Italy
| | | | - Sabino Iliceto
- Department of Cardiac, Thoracic and Vascular Sciences, Padua University Medical School, 35100 Padua, Italy; (S.I.); (F.T.)
| | - Paolo Simioni
- Department of Medicine, Thrombotic and Haemorrhagic Diseases Unit, Veneto Region Haemophilia and Thrombophilia Centre, University of Padua Medical School, 35100 Padua, Italy;
| | - Francesco Tona
- Department of Cardiac, Thoracic and Vascular Sciences, Padua University Medical School, 35100 Padua, Italy; (S.I.); (F.T.)
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Thackston KA, Deheyn DD, Sievenpiper DF. Limitations on electromagnetic communication by vibrational resonances in biological systems. Phys Rev E 2020; 101:062401. [PMID: 32688526 DOI: 10.1103/physreve.101.062401] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2019] [Accepted: 04/30/2020] [Indexed: 11/07/2022]
Abstract
Previous research in biology and physics speculates that high-frequency electromagnetic fields may be an unexplored method of cellular and subcellular communication. The predominant theory for generating electric fields in the cell is mechanical vibration of charged or polar biomolecules such as cell membranes or microtubules. The challenge to this theory is explaining how high-frequency vibrations would not be overdamped by surrounding biological media. As many of these suspected resonators are too large for atomistic molecular dynamics simulations, accurately modeling biological resonators remains an ongoing challenge. While many resonators have been studied and simulated, the general limitations on communication imposed by energy transfer arguments have not been considered. Starting with energy transfer expressions from coupled-mode theory, we derive expressions for the minimum quality factor (Q factor) required to sustain communication for both near- and far-field interactions. We compare previous simulation studies and our theory. We determine the flexing mode of microtubules as an identified resonance in the literature which meets our criteria. Our results suggest the major obstacle to meeting our criteria for effective electromagnetic communication is the trade-off between the Q factor and the plasma frequency: Resonators must be large enough to have a large Q factor, but small enough to resonate at frequencies greater than the plasma frequency.
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Affiliation(s)
- Kyle A Thackston
- Department of Electrical Engineering, University of California San Diego, San Diego, California 92161, USA
| | - Dimitri D Deheyn
- Scripps Institution of Oceanography, University of California San Diego, La Jolla, California 92037, USA
| | - Daniel F Sievenpiper
- Department of Electrical Engineering, University of California San Diego, San Diego, California 92161, USA
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5
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Graybill PM, Davalos RV. Cytoskeletal Disruption after Electroporation and Its Significance to Pulsed Electric Field Therapies. Cancers (Basel) 2020; 12:E1132. [PMID: 32366043 PMCID: PMC7281591 DOI: 10.3390/cancers12051132] [Citation(s) in RCA: 38] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2020] [Revised: 04/24/2020] [Accepted: 04/27/2020] [Indexed: 12/18/2022] Open
Abstract
Pulsed electric fields (PEFs) have become clinically important through the success of Irreversible Electroporation (IRE), Electrochemotherapy (ECT), and nanosecond PEFs (nsPEFs) for the treatment of tumors. PEFs increase the permeability of cell membranes, a phenomenon known as electroporation. In addition to well-known membrane effects, PEFs can cause profound cytoskeletal disruption. In this review, we summarize the current understanding of cytoskeletal disruption after PEFs. Compiling available studies, we describe PEF-induced cytoskeletal disruption and possible mechanisms of disruption. Additionally, we consider how cytoskeletal alterations contribute to cell-cell and cell-substrate disruption. We conclude with a discussion of cytoskeletal disruption-induced anti-vascular effects of PEFs and consider how a better understanding of cytoskeletal disruption after PEFs may lead to more effective therapies.
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Affiliation(s)
- Philip M. Graybill
- BEMS Lab, Department of Biomedical Engineering and Mechanics, Virginia Tech, Blacksburg, VA 24061, USA;
- Department of Mechanical Engineering, Virginia Tech, Blacksburg, VA 24061, USA
| | - Rafael V. Davalos
- BEMS Lab, Department of Biomedical Engineering and Mechanics, Virginia Tech, Blacksburg, VA 24061, USA;
- Department of Mechanical Engineering, Virginia Tech, Blacksburg, VA 24061, USA
- Virginia Tech–Wake Forest University, School of Biomedical Engineering and Sciences, Blacksburg, VA 24061, USA
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Abstract
Biological systems have evolved biochemical, electrical, mechanical, and genetic networks to perform essential functions across various length and time scales. High-aspect-ratio biological nanowires, such as bacterial pili and neurites, mediate many of the interactions and homeostasis in and between these networks. Synthetic materials designed to mimic the structure of biological nanowires could also incorporate similar functional properties, and exploiting this structure-function relationship has already proved fruitful in designing biointerfaces. Semiconductor nanowires are a particularly promising class of synthetic nanowires for biointerfaces, given (1) their unique optical and electronic properties and (2) their high degree of synthetic control and versatility. These characteristics enable fabrication of a variety of electronic and photonic nanowire devices, allowing for the formation of well-defined, functional bioelectric interfaces at the biomolecular level to the whole-organ level. In this Focus Review, we first discuss the history of bioelectric interfaces with semiconductor nanowires. We next highlight several important, endogenous biological nanowires and use these as a framework to categorize semiconductor nanowire-based biointerfaces. Within this framework we then review the fundamentals of bioelectric interfaces with semiconductor nanowires and comment on both material choice and device design to form biointerfaces spanning multiple length scales. We conclude with a discussion of areas with the potential for greatest impact using semiconductor nanowire-enabled biointerfaces in the future.
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Affiliation(s)
- Bozhi Tian
- Department of Chemistry, the University of Chicago, Chicago, IL USA
- The James Franck Institute, the University of Chicago, Chicago, IL USA
- The Institute for Biophysical Dynamics, Chicago, IL USA
| | - Charles M. Lieber
- Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA, USA
- Center for Brain Science, Harvard University, Cambridge, MA, USA
- John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, USA
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Thackston KA, Deheyn DD, Sievenpiper DF. Simulation of electric fields generated from microtubule vibrations. Phys Rev E 2019; 100:022410. [PMID: 31574607 DOI: 10.1103/physreve.100.022410] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2019] [Indexed: 06/10/2023]
Abstract
Microtubules are tubular proteins that form part of the cytoskeleton in eukaryotic cells. Because of their unique mechanical properties, many studies have theorized microtubules could show high-frequency mechanical vibrations. Others have further suggested these vibrations of the electrically polar microtubules could be a source of electric fields inside the cell that could serve some biological function, such as a role in organizing mitosis or also possibly in cell-to-cell communication. In this work, we use a transient method to simulate the electric fields that would be generated from a single microtubule supposing they could sustain vibrations. We evaluate the biological significance of the electric fields and the potential energy microtubules might exert on one another. Our simulation method allows us to evaluate vibrational modes that have not previously been studied. The simulations suggest the acoustic branch flexing mode would actually be the most electrically active. Our results suggest a single vibrating microtubule could potentially exert significant forces (those that exceed thermal energy) on biological dipoles or charges at distances larger then the Debye length, on the order of 10nm from the surface of the microtubule, but interaction is not likely at greater distances.
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Affiliation(s)
- Kyle A Thackston
- Electrical Engineering Department, University of California, San Diego, California 92093, USA
| | - Dimitri D Deheyn
- Scripps Institution of Oceanography, University of California, San Diego, California 92093, USA
| | - Daniel F Sievenpiper
- Electrical Engineering Department, University of California, San Diego, California 92093, USA
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8
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Facchin F, Canaider S, Tassinari R, Zannini C, Bianconi E, Taglioli V, Olivi E, Cavallini C, Tausel M, Ventura C. Physical energies to the rescue of damaged tissues. World J Stem Cells 2019; 11:297-321. [PMID: 31293714 PMCID: PMC6600852 DOI: 10.4252/wjsc.v11.i6.297] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/09/2019] [Revised: 04/24/2019] [Accepted: 05/29/2019] [Indexed: 02/06/2023] Open
Abstract
Rhythmic oscillatory patterns sustain cellular dynamics, driving the concerted action of regulatory molecules, microtubules, and molecular motors. We describe cellular microtubules as oscillators capable of synchronization and swarming, generating mechanical and electric patterns that impact biomolecular recognition. We consider the biological relevance of seeing the inside of cells populated by a network of molecules that behave as bioelectronic circuits and chromophores. We discuss the novel perspectives disclosed by mechanobiology, bioelectromagnetism, and photobiomodulation, both in term of fundamental basic science and in light of the biomedical implication of using physical energies to govern (stem) cell fate. We focus on the feasibility of exploiting atomic force microscopy and hyperspectral imaging to detect signatures of nanomotions and electromagnetic radiation (light), respectively, generated by the stem cells across the specification of their multilineage repertoire. The chance is reported of using these signatures and the diffusive features of physical waves to direct specifically the differentiation program of stem cells in situ, where they already are resident in all the tissues of the human body. We discuss how this strategy may pave the way to a regenerative and precision medicine without the needs for (stem) cell or tissue transplantation. We describe a novel paradigm based upon boosting our inherent ability for self-healing.
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Affiliation(s)
- Federica Facchin
- Department of Experimental, Diagnostic and Specialty Medicine (DIMES), School of Medicine, University of Bologna, Bologna 40100, Italy
- National Laboratory of Molecular Biology and Stem Cell Engineering, National Institute of Biostructures and Biosystems, CNR, Bologna 40100, Italy
| | - Silvia Canaider
- Department of Experimental, Diagnostic and Specialty Medicine (DIMES), School of Medicine, University of Bologna, Bologna 40100, Italy
- National Laboratory of Molecular Biology and Stem Cell Engineering, National Institute of Biostructures and Biosystems, CNR, Bologna 40100, Italy
| | - Riccardo Tassinari
- National Laboratory of Molecular Biology and Stem Cell Engineering, National Institute of Biostructures and Biosystems, CNR, Bologna 40100, Italy
| | - Chiara Zannini
- National Laboratory of Molecular Biology and Stem Cell Engineering, National Institute of Biostructures and Biosystems, CNR, Bologna 40100, Italy
| | - Eva Bianconi
- National Laboratory of Molecular Biology and Stem Cell Engineering, National Institute of Biostructures and Biosystems, CNR, Bologna 40100, Italy
| | - Valentina Taglioli
- National Laboratory of Molecular Biology and Stem Cell Engineering, National Institute of Biostructures and Biosystems, CNR, Bologna 40100, Italy
| | - Elena Olivi
- National Laboratory of Molecular Biology and Stem Cell Engineering, National Institute of Biostructures and Biosystems, CNR, Bologna 40100, Italy
| | - Claudia Cavallini
- National Laboratory of Molecular Biology and Stem Cell Engineering, National Institute of Biostructures and Biosystems, CNR, Bologna 40100, Italy
| | | | - Carlo Ventura
- Department of Experimental, Diagnostic and Specialty Medicine (DIMES), School of Medicine, University of Bologna, Bologna 40100, Italy
- National Laboratory of Molecular Biology and Stem Cell Engineering, National Institute of Biostructures and Biosystems, CNR, Bologna 40100, Italy.
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Grasso G, Rebella M, Morbiducci U, Tuszynski JA, Danani A, Deriu MA. The Role of Structural Polymorphism in Driving the Mechanical Performance of the Alzheimer's Beta Amyloid Fibrils. Front Bioeng Biotechnol 2019; 7:83. [PMID: 31106199 PMCID: PMC6499180 DOI: 10.3389/fbioe.2019.00083] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2019] [Accepted: 04/03/2019] [Indexed: 11/13/2022] Open
Abstract
Alzheimer's Disease (AD) is related with the abnormal aggregation of amyloid β-peptides Aβ1−40 and Aβ1−42, the latter having a polymorphic character which gives rise to U- or S-shaped fibrils. Elucidating the role played by the nanoscale-material architecture on the amyloid fibril stability is a crucial breakthrough to better understand the pathological nature of amyloid structures and to support the rational design of bio-inspired materials. The computational study here presented highlights the superior mechanical behavior of the S-architecture, characterized by a Young's modulus markedly higher than the U-shaped architecture. The S-architecture showed a higher mechanical resistance to the enforced deformation along the fibril axis, consequence of a better interchain hydrogen bonds' distribution. In conclusion, this study, focusing the attention on the pivotal multiscale relationship between molecular phenomena and material properties, suggests the S-shaped Aβ1−42 species as a target of election in computational screen/design/optimization of effective aggregation modulators.
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Affiliation(s)
- Gianvito Grasso
- Istituto Dalle Molle di studi sull'Intelligenza Artificiale, Scuola Universitaria Professionale della Svizzera Italiana, Università della Svizzera Italiana, Manno, Switzerland
| | - Martina Rebella
- Polito BioMEDLab, Department of Mechanical and Aerospace Engineering, Politecnico di Torino, Turin, Italy
| | - Umberto Morbiducci
- Polito BioMEDLab, Department of Mechanical and Aerospace Engineering, Politecnico di Torino, Turin, Italy
| | - Jack A Tuszynski
- Polito BioMEDLab, Department of Mechanical and Aerospace Engineering, Politecnico di Torino, Turin, Italy.,Department of Physics, University of Alberta, Edmonton AB, Canada
| | - Andrea Danani
- Istituto Dalle Molle di studi sull'Intelligenza Artificiale, Scuola Universitaria Professionale della Svizzera Italiana, Università della Svizzera Italiana, Manno, Switzerland
| | - Marco A Deriu
- Istituto Dalle Molle di studi sull'Intelligenza Artificiale, Scuola Universitaria Professionale della Svizzera Italiana, Università della Svizzera Italiana, Manno, Switzerland
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Correction: Electro-Acoustic Behavior of the Mitotic Spindle: A Semi-Classical Coarse-Grained Model. PLoS One 2019; 14:e0210897. [PMID: 30689638 PMCID: PMC6349308 DOI: 10.1371/journal.pone.0210897] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
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Barvitenko N, Lawen A, Aslam M, Pantaleo A, Saldanha C, Skverchinskaya E, Regolini M, Tuszynski JA. Integration of intracellular signaling: Biological analogues of wires, processors and memories organized by a centrosome 3D reference system. Biosystems 2018; 173:191-206. [PMID: 30142359 DOI: 10.1016/j.biosystems.2018.08.007] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2018] [Revised: 08/03/2018] [Accepted: 08/20/2018] [Indexed: 02/07/2023]
Abstract
BACKGROUND Myriads of signaling pathways in a single cell function to achieve the highest spatio-temporal integration. Data are accumulating on the role of electromechanical soliton-like waves in signal transduction processes. Theoretical studies strongly suggest feasibility of both classical and quantum computing involving microtubules. AIM A theoretical study of the role of the complex composed of the plasma membrane and the microtubule-based cytoskeleton as a system that transmits, stores and processes information. METHODS Theoretical analysis presented here refers to (i) the Penrose-Hameroff theory of consciousness (Orchestrated Objective Reduction; Orch OR), (ii) the description of the centrosome as a reference system for construction of the 3D map of the cell proposed by Regolini, (iii) the Heimburg-Jackson model of the nerve pulse propagation along axons' lipid bilayer as soliton-like electro-mechanical waves. RESULTS AND CONCLUSION The ideas presented in this paper provide a qualitative model for the decision-making processes in a living cell undergoing a differentiation process. OUTLOOK This paper paves the way for the real-time live-cell observation of information processing by microtubule-based cytoskeleton and cell fate decision making.
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Affiliation(s)
| | - Alfons Lawen
- Monash University, School of Biomedical Sciences, Department of Biochemistry and Molecular Biology, VIC, 3800, Australia
| | - Muhammad Aslam
- Medical Clininc I, Cardiology/Angiology, University Hospital, Justus-Liebig-University, Giessen, Germany
| | - Antonella Pantaleo
- Department of Biomedical Sciences, University of Sassari, Sassari, Italy
| | - Carlota Saldanha
- Instituto de Medicina Molecular, Instituto de Bioquimica, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal
| | | | - Marco Regolini
- Department of Bioengineering and Mathematical Modeling, AudioLogic, Milan, Italy
| | - Jack A Tuszynski
- Department of Oncology, University of Alberta, Edmonton, Alberta, Canada; Department of Physics, University of Alberta, Edmonton, Alberta, Canada; Department of Mechanical and Aerospace Engineering, Politecnico di Torino, Corso Duca degli Abruzzi 24, IT-10128, Torino, Italy.
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12
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On possible role of DNA electrodynamics in chromatin regulation. PROGRESS IN BIOPHYSICS AND MOLECULAR BIOLOGY 2018; 134:50-54. [DOI: 10.1016/j.pbiomolbio.2017.12.006] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/12/2017] [Revised: 12/22/2017] [Accepted: 12/27/2017] [Indexed: 12/23/2022]
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Grasso G, Muscat S, Rebella M, Morbiducci U, Audenino A, Danani A, Deriu MA. Cell penetrating peptide modulation of membrane biomechanics by Molecular dynamics. J Biomech 2018; 73:137-144. [PMID: 29631749 DOI: 10.1016/j.jbiomech.2018.03.036] [Citation(s) in RCA: 36] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2017] [Revised: 03/14/2018] [Accepted: 03/21/2018] [Indexed: 11/17/2022]
Abstract
The efficacy of a pharmaceutical treatment is often countered by the inadequate membrane permeability, that prevents drugs from reaching their specific intracellular targets. Cell penetrating peptides (CPPs) are able to route across cells' membrane various types of cargo, including drugs and nanoparticles. However, CPPs internalization mechanisms are not yet fully understood and depend on a wide variety of aspects. In this contest, the entry of a CPP into the lipid bilayer might induce molecular conformational changes, including marked variations on membrane's mechanical properties. Understanding how the CPP does influence the mechanical properties of cells membrane is crucial to design, engineer and improve new and existing penetrating peptides. Here, all atom Molecular Dynamics (MD) simulations were used to investigate the interaction between different types of CPPs embedded in a lipid bilayer of dioleoyl phosphatidylcholine (DOPC). In a greater detail, we systematically highlighted how CPP properties are responsible for modulating the membrane bending modulus. Our findings highlighted the CPP hydropathy strongly correlated with penetration of water molecules in the lipid bilayer, thus supporting the hypothesis that the amount of water each CPP can route inside the membrane is modulated by the hydrophobic and hydrophilic character of the peptide. Water penetration promoted by CPPs leads to a local decrease of the lipid order, which emerges macroscopically as a reduction of the membrane bending modulus.
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Affiliation(s)
- Gianvito Grasso
- Istituto Dalle Molle di Studi sull'Intelligenza Artificiale (IDSIA), Scuola universitaria professionale della Svizzera italiana (SUPSI), Università della Svizzera Italiana (USI), Centro Galleria 2, Manno CH-6928, Switzerland
| | - Stefano Muscat
- Department of Mechanical and Aerospace Engineering, Politecnico di Torino, Corso Duca degli Abruzzi 24, IT-10128 Torino, Italy
| | - Martina Rebella
- Department of Mechanical and Aerospace Engineering, Politecnico di Torino, Corso Duca degli Abruzzi 24, IT-10128 Torino, Italy
| | - Umberto Morbiducci
- Department of Mechanical and Aerospace Engineering, Politecnico di Torino, Corso Duca degli Abruzzi 24, IT-10128 Torino, Italy
| | - Alberto Audenino
- Department of Mechanical and Aerospace Engineering, Politecnico di Torino, Corso Duca degli Abruzzi 24, IT-10128 Torino, Italy
| | - Andrea Danani
- Istituto Dalle Molle di Studi sull'Intelligenza Artificiale (IDSIA), Scuola universitaria professionale della Svizzera italiana (SUPSI), Università della Svizzera Italiana (USI), Centro Galleria 2, Manno CH-6928, Switzerland
| | - Marco A Deriu
- Istituto Dalle Molle di Studi sull'Intelligenza Artificiale (IDSIA), Scuola universitaria professionale della Svizzera italiana (SUPSI), Università della Svizzera Italiana (USI), Centro Galleria 2, Manno CH-6928, Switzerland.
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14
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Rotenberg MY, Tian B. Talking to cells: semiconductor nanomaterials at the cellular interface. ADVANCED BIOSYSTEMS 2018; 2:1700242. [PMID: 30906852 PMCID: PMC6430216 DOI: 10.1002/adbi.201700242] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
The interface of biological components with semiconductors is a growing field with numerous applications. For example, the interfaces can be used to sense and modulate the electrical activity of single cells and tissues. From the materials point of view, silicon is the ideal option for such studies due to its controlled chemical synthesis, scalable lithography for functional devices, excellent electronic and optical properties, biocompatibility and biodegradability. Recent advances in this area are pushing the bio-interfaces from the tissue and organ level to the single cell and sub-cellular regimes. In this progress report, we will describe some fundamental studies focusing on miniaturizing the bioelectric and biomechanical interfaces. Additionally, many of our highlighted examples involve freestanding silicon-based nanoscale systems, in addition to substrate-bound structures or devices; the former offers new promise for basic research and clinical application. In this report, we will describe recent developments in the interfacing of neuronal and cardiac cells and their networks. Moreover, we will briefly discuss the incorporation of semiconductor nanostructures for interfacing non-excitable cells in applications such as probing intracellular force dynamics and drug delivery. Finally, we will suggest several directions for future exploration.
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Affiliation(s)
| | - Bozhi Tian
- The James Franck Institute, the University of Chicago, Chicago, IL 60637
- Department of Chemistry, the University of Chicago, Chicago, IL 60637
- The Institute for Biophysical Dynamics, Chicago, IL 60637
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15
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Wenger C, Miranda PC, Salvador R, Thielscher A, Bomzon Z, Giladi M, Mrugala MM, Korshoej AR. A Review on Tumor-Treating Fields (TTFields): Clinical Implications Inferred From Computational Modeling. IEEE Rev Biomed Eng 2018; 11:195-207. [DOI: 10.1109/rbme.2017.2765282] [Citation(s) in RCA: 46] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
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16
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Igamberdiev AU, Shklovskiy-Kordi NE. The quantum basis of spatiotemporality in perception and consciousness. PROGRESS IN BIOPHYSICS AND MOLECULAR BIOLOGY 2017; 130:15-25. [PMID: 28232245 DOI: 10.1016/j.pbiomolbio.2017.02.008] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/01/2016] [Accepted: 02/16/2017] [Indexed: 12/21/2022]
Abstract
Living systems inhabit the area of the world which is shaped by the predictable space-time of physical objects and forces that can be incorporated into their perception pattern. The process of selecting a "habitable" space-time is the internal quantum measurement in which living systems become embedded into the environment that supports their living state. This means that living organisms choose a coordinate system in which the influence of measurement is minimal. We discuss specific roles of biological macromolecules, in particular of the cytoskeleton, in shaping perception patterns formed in the internal measurement process. Operation of neuron is based on the transmission of signals via cytoskeleton where the digital output is generated that can be decoded through a reflective action of the perceiving agent. It is concluded that the principle of optimality in biology as formulated by Liberman et al. (BioSystems 22, 135-154, 1989) is related to the establishment of spatiotemporal patterns that are maximally predictable and can hold the living state for a prolonged time. This is achieved by the selection of a habitable space approximated to the conditions described by classical physics.
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Affiliation(s)
- Abir U Igamberdiev
- Department of Biology, Memorial University of Newfoundland, St. John's, NL A1B 3X9, Canada.
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17
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Carr L, Bardet SM, Burke RC, Arnaud-Cormos D, Leveque P, O'Connor RP. Calcium-independent disruption of microtubule dynamics by nanosecond pulsed electric fields in U87 human glioblastoma cells. Sci Rep 2017; 7:41267. [PMID: 28117459 PMCID: PMC5259788 DOI: 10.1038/srep41267] [Citation(s) in RCA: 39] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2016] [Accepted: 12/19/2016] [Indexed: 12/26/2022] Open
Abstract
High powered, nanosecond duration, pulsed electric fields (nsPEF) cause cell death by a mechanism that is not fully understood and have been proposed as a targeted cancer therapy. Numerous chemotherapeutics work by disrupting microtubules. As microtubules are affected by electrical fields, this study looks at the possibility of disrupting them electrically with nsPEF. Human glioblastoma cells (U87-MG) treated with 100, 10 ns, 44 kV/cm pulses at a frequency of 10 Hz showed a breakdown of their interphase microtubule network that was accompanied by a reduction in the number of growing microtubules. This effect is temporally linked to loss of mitochondrial membrane potential and independent of cellular swelling and calcium influx, two factors that disrupt microtubule growth dynamics. Super-resolution microscopy revealed microtubule buckling and breaking as a result of nsPEF application, suggesting that nsPEF may act directly on microtubules.
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Affiliation(s)
- Lynn Carr
- XLIM Research Institute, UMR CNRS No 7252, University of Limoges, Faculty of Science and Techniques, 123 Avenue Albert Thomas, 87060 Limoges, France
| | - Sylvia M Bardet
- XLIM Research Institute, UMR CNRS No 7252, University of Limoges, Faculty of Science and Techniques, 123 Avenue Albert Thomas, 87060 Limoges, France
| | - Ryan C Burke
- XLIM Research Institute, UMR CNRS No 7252, University of Limoges, Faculty of Science and Techniques, 123 Avenue Albert Thomas, 87060 Limoges, France
| | - Delia Arnaud-Cormos
- XLIM Research Institute, UMR CNRS No 7252, University of Limoges, Faculty of Science and Techniques, 123 Avenue Albert Thomas, 87060 Limoges, France
| | - Philippe Leveque
- XLIM Research Institute, UMR CNRS No 7252, University of Limoges, Faculty of Science and Techniques, 123 Avenue Albert Thomas, 87060 Limoges, France
| | - Rodney P O'Connor
- XLIM Research Institute, UMR CNRS No 7252, University of Limoges, Faculty of Science and Techniques, 123 Avenue Albert Thomas, 87060 Limoges, France
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18
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Tuszynski JA, Wenger C, Friesen DE, Preto J. An Overview of Sub-Cellular Mechanisms Involved in the Action of TTFields. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2016; 13:E1128. [PMID: 27845746 PMCID: PMC5129338 DOI: 10.3390/ijerph13111128] [Citation(s) in RCA: 58] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/26/2016] [Revised: 10/23/2016] [Accepted: 11/07/2016] [Indexed: 12/13/2022]
Abstract
Long-standing research on electric and electromagnetic field interactions with biological cells and their subcellular structures has mainly focused on the low- and high-frequency regimes. Biological effects at intermediate frequencies between 100 and 300 kHz have been recently discovered and applied to cancer cells as a therapeutic modality called Tumor Treating Fields (TTFields). TTFields are clinically applied to disrupt cell division, primarily for the treatment of glioblastoma multiforme (GBM). In this review, we provide an assessment of possible physical interactions between 100 kHz range alternating electric fields and biological cells in general and their nano-scale subcellular structures in particular. This is intended to mechanistically elucidate the observed strong disruptive effects in cancer cells. Computational models of isolated cells subject to TTFields predict that for intermediate frequencies the intracellular electric field strength significantly increases and that peak dielectrophoretic forces develop in dividing cells. These findings are in agreement with in vitro observations of TTFields' disruptive effects on cellular function. We conclude that the most likely candidates to provide a quantitative explanation of these effects are ionic condensation waves around microtubules as well as dielectrophoretic effects on the dipole moments of microtubules. A less likely possibility is the involvement of actin filaments or ion channels.
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Affiliation(s)
- Jack A Tuszynski
- Department of Oncology, University of Alberta, Edmonton, AB T6G 1Z2, Canada.
- Department of Physics, University of Alberta, Edmonton, AB T6G 2E1, Canada.
| | - Cornelia Wenger
- The Institute of Biophysics and Biomedical Engineering, Faculdade de Ciências, Universidade de Lisboa, Lisboa 1749-016, Portugal.
| | - Douglas E Friesen
- Department of Oncology, University of Alberta, Edmonton, AB T6G 1Z2, Canada.
| | - Jordane Preto
- Department of Oncology, University of Alberta, Edmonton, AB T6G 1Z2, Canada.
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19
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Pokorný J, Pokorný J, Foletti A, Kobilková J, Vrba J, Vrba J. Mitochondrial Dysfunction and Disturbed Coherence: Gate to Cancer. Pharmaceuticals (Basel) 2015; 8:675-95. [PMID: 26437417 PMCID: PMC4695805 DOI: 10.3390/ph8040675] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2015] [Revised: 09/06/2015] [Accepted: 09/11/2015] [Indexed: 12/21/2022] Open
Abstract
Continuous energy supply, a necessary condition for life, excites a state far from thermodynamic equilibrium, in particular coherent electric polar vibrations depending on water ordering in the cell. Disturbances in oxidative metabolism and coherence are a central issue in cancer development. Oxidative metabolism may be impaired by decreased pyruvate transfer to the mitochondrial matrix, either by parasitic consumption and/or mitochondrial dysfunction. This can in turn lead to disturbance in water molecules’ ordering, diminished power, and coherence of the electromagnetic field. In tumors with the Warburg (reverse Warburg) effect, mitochondrial dysfunction affects cancer cells (fibroblasts associated with cancer cells), and the electromagnetic field generated by microtubules in cancer cells has low power (high power due to transport of energy-rich metabolites from fibroblasts), disturbed coherence, and a shifted frequency spectrum according to changed power. Therapeutic strategies restoring mitochondrial function may trigger apoptosis in treated cells; yet, before this step is performed, induction (inhibition) of pyruvate dehydrogenase kinases (phosphatases) may restore the cancer state. In tumor tissues with the reverse Warburg effect, Caveolin-1 levels should be restored and the transport of energy-rich metabolites interrupted to cancer cells. In both cancer phenotypes, achieving permanently reversed mitochondrial dysfunction with metabolic-modulating drugs may be an effective, specific anti-cancer strategy.
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Affiliation(s)
- Jiří Pokorný
- Institute of Photonics and Electronics, Czech Academy of Sciences, Chaberská 57, 182 51 Prague 8, Czech Republic.
| | - Jan Pokorný
- Institute of Physics, Czech Academy of Sciences, Na Slovance 2, 182 21 Prague 8, Czech Republic.
| | - Alberto Foletti
- Institute of Translational Pharmacology, National Research Council-CNR, Via Fosso del Cavaliere 100, Rome 00133, Italy.
- Clinical Biophysics International Research Group, via Maggio 21, Lugano 6900, Switzerland.
| | - Jitka Kobilková
- Department of Obstetrics and Gynaecology, 1st Faculty of Medicine, Charles University in Prague, Apolinářská 18, 128 00 Prague 2, Czech Republic.
| | - Jan Vrba
- Faculty of Electrical Engineering, Czech Technical University in Prague, Technická 2, 166 27 Prague 6, Czech Republic.
| | - Jan Vrba
- Faculty of Biomedical Engineering, Czech Technical University in Kladno, Sitná Square 3105, 272 01 Kladno, Czech Republic.
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