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Biophysics and Mechanical Properties of Cells 2.0

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Biophysics".

Deadline for manuscript submissions: closed (31 January 2024) | Viewed by 3706

Special Issue Editor


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Guest Editor
Department of Engineering and Architecture, Università degli Studi di Trieste, Trieste, Italy
Interests: biophysics and mechanical properties of cells
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This Special Issue is the second volume of our previous Special Issue "Biophysics and Mechanical Properties of Cells". 

Cells in our body are subjected to mechanical stresses and can sense these mechanical stimuli and actively respond to them by triggering biomechanical reactions that include cell growth, proliferation, differentiation, motility, and even apoptosis. Furthermore, cell mechanics studies have shown that changes in cell and nuclear mechanics are hallmarks of many diseases, such as cardiovascular disease, laminopathies, cancer, infectious diseases, and fragility in aging. In this regard, mechanobiology studies the essential roles that these physical factors play via mechanotransduction. However, this field needs reliable and reproducible data of cell mechanical properties, but reported values of cell stiffness and/or viscosity vary considerably, which suggests differences in how the results of different methods are obtained or analyzed by different groups.

Therefore, we believe that the present offers an excellent opportunity to gain a better understanding of these fundamental concepts, and we would like to give researchers in many interdisciplinary areas of research—such as biophysics, biomedicine, tissue engineering, and materials science—the opportunity to address and illustrate the complementarity of biophysical and biological approaches and how mechanical properties influence cells' behavior with their surrounding microenvironment, both in healthy conditions and in diseases. Recent advances in developing novel techniques and tools for cell mechanics characterization and the challenges associated with their implementation will also be presented.

Prof. Dr. Orfeo Sbaizero
Guest Editor

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

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Keywords

  • cell mechanics
  • cell surface mechanics 
  • intracellular mechanics
  • mechanobiology
  • mechanotransduction
  • mechanosensing
  • modelling cell mechanic
  • cell mechanical techniques 
  • exogenous mechanical stimuli
  • endogenous mechanical stimuli

Published Papers (3 papers)

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Research

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12 pages, 637 KiB  
Communication
Size Matters: Rethinking Hertz Model Interpretation for Cell Mechanics Using AFM
by Katarína Mendová, Martin Otáhal, Mitja Drab and Matej Daniel
Int. J. Mol. Sci. 2024, 25(13), 7186; https://doi.org/10.3390/ijms25137186 - 29 Jun 2024
Viewed by 225
Abstract
Cell mechanics are a biophysical indicator of cell state, such as cancer metastasis, leukocyte activation, and cell cycle progression. Atomic force microscopy (AFM) is a widely used technique to measure cell mechanics, where the Young modulus of a cell is usually derived from [...] Read more.
Cell mechanics are a biophysical indicator of cell state, such as cancer metastasis, leukocyte activation, and cell cycle progression. Atomic force microscopy (AFM) is a widely used technique to measure cell mechanics, where the Young modulus of a cell is usually derived from the Hertz contact model. However, the Hertz model assumes that the cell is an elastic, isotropic, and homogeneous material and that the indentation is small compared to the cell size. These assumptions neglect the effects of the cytoskeleton, cell size and shape, and cell environment on cell deformation. In this study, we investigated the influence of cell size on the estimated Young’s modulus using liposomes as cell models. Liposomes were prepared with different sizes and filled with phosphate buffered saline (PBS) or hyaluronic acid (HA) to mimic the cytoplasm. AFM was used to obtain the force indentation curves and fit them to the Hertz model. We found that the larger the liposome, the lower the estimated Young’s modulus for both PBS-filled and HA-filled liposomes. This suggests that the Young modulus obtained from the Hertz model is not only a property of the cell material but also depends on the cell dimensions. Therefore, when comparing or interpreting cell mechanics using the Hertz model, it is essential to account for cell size. Full article
(This article belongs to the Special Issue Biophysics and Mechanical Properties of Cells 2.0)
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18 pages, 2603 KiB  
Article
Defective Biomechanics and Pharmacological Rescue of Human Cardiomyocytes with Filamin C Truncations
by Marco Lazzarino, Michele Zanetti, Suet Nee Chen, Shanshan Gao, Brisa Peña, Chi Keung Lam, Joseph C. Wu, Matthew R. G. Taylor, Luisa Mestroni and Orfeo Sbaizero
Int. J. Mol. Sci. 2024, 25(5), 2942; https://doi.org/10.3390/ijms25052942 - 3 Mar 2024
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Abstract
Actin-binding filamin C (FLNC) is expressed in cardiomyocytes, where it localizes to Z-discs, sarcolemma, and intercalated discs. Although FLNC truncation variants (FLNCtv) are an established cause of arrhythmias and heart failure, changes in biomechanical properties of cardiomyocytes are mostly unknown. Thus, [...] Read more.
Actin-binding filamin C (FLNC) is expressed in cardiomyocytes, where it localizes to Z-discs, sarcolemma, and intercalated discs. Although FLNC truncation variants (FLNCtv) are an established cause of arrhythmias and heart failure, changes in biomechanical properties of cardiomyocytes are mostly unknown. Thus, we investigated the mechanical properties of human-induced pluripotent stem cells-derived cardiomyocytes (hiPSC-CMs) carrying FLNCtv. CRISPR/Cas9 genome-edited homozygous FLNCKO−/− hiPSC-CMs and heterozygous knock-out FLNCKO+/− hiPSC-CMs were analyzed and compared to wild-type FLNC (FLNCWT) hiPSC-CMs. Atomic force microscopy (AFM) was used to perform micro-indentation to evaluate passive and dynamic mechanical properties. A qualitative analysis of the beating traces showed gene dosage-dependent-manner “irregular” peak profiles in FLNCKO+/− and FLNCKO−/− hiPSC-CMs. Two Young’s moduli were calculated: E1, reflecting the compression of the plasma membrane and actin cortex, and E2, including the whole cell with a cytoskeleton and nucleus. Both E1 and E2 showed decreased stiffness in mutant FLNCKO+/− and FLNCKO−/− iPSC-CMs compared to that in FLNCWT. The cell adhesion force and work of adhesion were assessed using the retraction curve of the SCFS. Mutant FLNC iPSC-CMs showed gene dosage-dependent decreases in the work of adhesion and adhesion forces from the heterozygous FLNCKO+/− to the FLNCKO−/− model compared to FLNCWT, suggesting damaged cytoskeleton and membrane structures. Finally, we investigated the effect of crenolanib on the mechanical properties of hiPSC-CMs. Crenolanib is an inhibitor of the Platelet-Derived Growth Factor Receptor α (PDGFRA) pathway which is upregulated in FLNCtv hiPSC-CMs. Crenolanib was able to partially rescue the stiffness of FLNCKO−/− hiPSC-CMs compared to control, supporting its potential therapeutic role. Full article
(This article belongs to the Special Issue Biophysics and Mechanical Properties of Cells 2.0)
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Review

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37 pages, 2797 KiB  
Review
The Role of Mechanotransduction in Contact Inhibition of Locomotion and Proliferation
by Fumihiko Nakamura
Int. J. Mol. Sci. 2024, 25(4), 2135; https://doi.org/10.3390/ijms25042135 - 10 Feb 2024
Cited by 1 | Viewed by 1912
Abstract
Contact inhibition (CI) represents a crucial tumor-suppressive mechanism responsible for controlling the unbridled growth of cells, thus preventing the formation of cancerous tissues. CI can be further categorized into two distinct yet interrelated components: CI of locomotion (CIL) and CI of proliferation (CIP). [...] Read more.
Contact inhibition (CI) represents a crucial tumor-suppressive mechanism responsible for controlling the unbridled growth of cells, thus preventing the formation of cancerous tissues. CI can be further categorized into two distinct yet interrelated components: CI of locomotion (CIL) and CI of proliferation (CIP). These two components of CI have historically been viewed as separate processes, but emerging research suggests that they may be regulated by both distinct and shared pathways. Specifically, recent studies have indicated that both CIP and CIL utilize mechanotransduction pathways, a process that involves cells sensing and responding to mechanical forces. This review article describes the role of mechanotransduction in CI, shedding light on how mechanical forces regulate CIL and CIP. Emphasis is placed on filamin A (FLNA)-mediated mechanotransduction, elucidating how FLNA senses mechanical forces and translates them into crucial biochemical signals that regulate cell locomotion and proliferation. In addition to FLNA, trans-acting factors (TAFs), which are proteins or regulatory RNAs capable of directly or indirectly binding to specific DNA sequences in distant genes to regulate gene expression, emerge as sensitive players in both the mechanotransduction and signaling pathways of CI. This article presents methods for identifying these TAF proteins and profiling the associated changes in chromatin structure, offering valuable insights into CI and other biological functions mediated by mechanotransduction. Finally, it addresses unanswered research questions in these fields and delineates their possible future directions. Full article
(This article belongs to the Special Issue Biophysics and Mechanical Properties of Cells 2.0)
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