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Biomechanics of Cell Membrane

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 (15 November 2019) | Viewed by 25638

Special Issue Editors

Department of Nanobiotechnology (DNBT), Institute for Biophysics, BOKU University for Natural Resources and Life Sciences, Muthgasse 11 (Simon Zeisel Haus), A-1190 Vienna, Austria
Interests: physical chemistry; colloids and interfaces; scanning probe microscopy; spectroscopy; surface analytical techniques; mechanical properties of biomaterials; soft matter
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear colleagues,

This Special Issue will focus on measuring and characterizing the mechanical and adhesive properties of cells and membranes using different techniques such scanning force microscopy, laser pinzette, optical tweezers and many others. Topics of interest include but are not limited to studies of lipid membranes, erythrocytes, and endothelial cells. Characterizing and measuring the properties and behavior of cells present a major challenge to researchers in this field. In this issue, the principles and techniques used in studies of cell biomechanics will be one of main themes. The publication of original articles will contribute to progress in the area of Nano/Biomechanics, and will further stimulate progress in understanding the link between the mechanical properties of cells and membranes and the physio-biological mechanisms involved.

Prof. Dr. Stefano Leporatti
Prof. Dr. Jose L. Toca-Herrera
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

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

  • biomechanics
  • cell membranes
  • scanning force microscopy
  • optical tweezers
  • laser pinzette

Published Papers (7 papers)

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Editorial

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3 pages, 185 KiB  
Editorial
Biomechanics of Cell Membrane
by Stefano Leporatti and José L. Toca-Herrera
Int. J. Mol. Sci. 2020, 21(15), 5413; https://doi.org/10.3390/ijms21155413 - 30 Jul 2020
Viewed by 2284
Abstract
This Special Issue is focused on measuring and characterizing the mechanical and adhesive properties of cells and membranes [...] Full article
(This article belongs to the Special Issue Biomechanics of Cell Membrane)

Research

Jump to: Editorial

16 pages, 2941 KiB  
Article
Mechanical Model for Catch-Bond-Mediated Cell Adhesion in Shear Flow
by Long Li, Wei Kang and Jizeng Wang
Int. J. Mol. Sci. 2020, 21(2), 584; https://doi.org/10.3390/ijms21020584 - 16 Jan 2020
Cited by 7 | Viewed by 3305
Abstract
Catch bond, whose lifetime increases with applied tensile force, can often mediate rolling adhesion of cells in a hydrodynamic environment. However, the mechanical mechanism governing the kinetics of rolling adhesion of cells through catch-bond under shear flow is not yet clear. In this [...] Read more.
Catch bond, whose lifetime increases with applied tensile force, can often mediate rolling adhesion of cells in a hydrodynamic environment. However, the mechanical mechanism governing the kinetics of rolling adhesion of cells through catch-bond under shear flow is not yet clear. In this study, a mechanical model is proposed for catch-bond-mediated cell adhesion in shear flow. The stochastic reaction of bond formation and dissociation is described as a Markovian process, whereas the dynamic motion of cells follows classical analytical mechanics. The steady state of cells significantly depends on the shear rate of flow. The upper and lower critical shear rates required for cell detachment and attachment are extracted, respectively. When the shear rate increases from the lower threshold to the upper threshold, cell rolling became slower and more regular, implying the flow-enhanced adhesion phenomenon. Our results suggest that this flow-enhanced stability of rolling adhesion is attributed to the competition between stochastic reactions of bonds and dynamics of cell rolling, instead of force lengthening the lifetime of catch bonds, thereby challenging the current view in understanding the mechanism behind this flow-enhanced adhesion phenomenon. Moreover, the loading history of flow defining bistability of cell adhesion in shear flow is predicted. These theoretical predictions are verified by Monte Carlo simulations and are related to the experimental observations reported in literature. Full article
(This article belongs to the Special Issue Biomechanics of Cell Membrane)
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17 pages, 4816 KiB  
Article
Ezrin Phosphorylation at T567 Modulates Cell Migration, Mechanical Properties, and Cytoskeletal Organization
by Xiaoli Zhang, Luis R. Flores, Michael C. Keeling, Kristina Sliogeryte and Núria Gavara
Int. J. Mol. Sci. 2020, 21(2), 435; https://doi.org/10.3390/ijms21020435 - 09 Jan 2020
Cited by 20 | Viewed by 3917
Abstract
Ezrin, a member of the ERM (ezrin/radixin/moesin) family of proteins, serves as a crosslinker between the plasma membrane and the actin cytoskeleton. By doing so, it provides structural links to strengthen the connection between the cell cortex and the plasma membrane, acting also [...] Read more.
Ezrin, a member of the ERM (ezrin/radixin/moesin) family of proteins, serves as a crosslinker between the plasma membrane and the actin cytoskeleton. By doing so, it provides structural links to strengthen the connection between the cell cortex and the plasma membrane, acting also as a signal transducer in multiple pathways during migration, proliferation, and endocytosis. In this study, we investigated the role of ezrin phosphorylation and its intracellular localization on cell motility, cytoskeleton organization, and cell stiffness, using fluorescence live-cell imaging, image quantification, and atomic force microscopy (AFM). Our results show that cells expressing constitutively active ezrin T567D (phosphomimetic) migrate faster and in a more directional manner, especially when ezrin accumulates at the cell rear. Similarly, image quantification results reveal that transfection with ezrin T567D alters the cell’s gross morphology and decreases cortical stiffness. In contrast, constitutively inactive ezrin T567A accumulates around the nucleus, and although it does not impair cell migration, it leads to a significant buildup of actin fibers, a decrease in nuclear volume, and an increase in cytoskeletal stiffness. Finally, cell transfection with the dominant negative ezrin FERM domain induces significant morphological and nuclear changes and affects actin, microtubules, and the intermediate filament vimentin, resulting in cytoskeletal fibers that are longer, thicker, and more aligned. Collectively, our results suggest that ezrin’s phosphorylation state and its intracellular localization plays a pivotal role in cell migration, modulating also biophysical properties, such as membrane–cortex linkage, cytoskeletal and nuclear organization, and the mechanical properties of cells. Full article
(This article belongs to the Special Issue Biomechanics of Cell Membrane)
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25 pages, 12185 KiB  
Article
Evidence for the Desmosomal Cadherin Desmoglein-3 in Regulating YAP and Phospho-YAP in Keratinocyte Responses to Mechanical Forces
by Jutamas Uttagomol, Usama Sharif Ahmad, Ambreen Rehman, Yunying Huang, Ana C. Laly, Angray Kang, Jan Soetaert, Randy Chance, Muy-Teck Teh, John T. Connelly and Hong Wan
Int. J. Mol. Sci. 2019, 20(24), 6221; https://doi.org/10.3390/ijms20246221 - 10 Dec 2019
Cited by 22 | Viewed by 4881
Abstract
Desmoglein 3 (Dsg3) plays a crucial role in cell-cell adhesion and tissue integrity. Increasing evidence suggests that Dsg3 acts as a regulator of cellular mechanotransduction, but little is known about its direct role in mechanical force transmission. The present study investigated the impact [...] Read more.
Desmoglein 3 (Dsg3) plays a crucial role in cell-cell adhesion and tissue integrity. Increasing evidence suggests that Dsg3 acts as a regulator of cellular mechanotransduction, but little is known about its direct role in mechanical force transmission. The present study investigated the impact of cyclic strain and substrate stiffness on Dsg3 expression and its role in mechanotransduction in keratinocytes. A direct comparison was made with E-cadherin, a well-characterized mechanosensor. Exposure of oral and skin keratinocytes to equiaxial cyclic strain promoted changes in the expression and localization of junction assembly proteins. The knockdown of Dsg3 by siRNA blocked strain-induced junctional remodeling of E-cadherin and Myosin IIa. Importantly, the study demonstrated that Dsg3 regulates the expression and localization of yes-associated protein (YAP), a mechanosensory, and an effector of the Hippo pathway. Furthermore, we showed that Dsg3 formed a complex with phospho-YAP and sequestered it to the plasma membrane, while Dsg3 depletion had an impact on both YAP and phospho-YAP in their response to mechanical forces, increasing the sensitivity of keratinocytes to the strain or substrate rigidity-induced nuclear relocation of YAP and phospho-YAP. Plakophilin 1 (PKP1) seemed to be crucial in recruiting the complex containing Dsg3/phospho-YAP to the cell surface since its silencing affected Dsg3 junctional assembly with concomitant loss of phospho-YAP at the cell periphery. Finally, we demonstrated that this Dsg3/YAP pathway has an influence on the expression of YAP1 target genes and cell proliferation. Together, these findings provide evidence of a novel role for Dsg3 in keratinocyte mechanotransduction. Full article
(This article belongs to the Special Issue Biomechanics of Cell Membrane)
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15 pages, 3435 KiB  
Article
Acute Cytotoxic Effects on Morphology and Mechanical Behavior in MCF-7 Induced by TiO2NPs Exposure
by Mariafrancesca Cascione, Valeria De Matteis, Giacomo Mandriota, Stefano Leporatti and Rosaria Rinaldi
Int. J. Mol. Sci. 2019, 20(14), 3594; https://doi.org/10.3390/ijms20143594 - 23 Jul 2019
Cited by 7 | Viewed by 3428
Abstract
The side effects induced by nanoparticle exposure at a cellular level are one of the priority research topics due to the steady increase in the use of nanoparticles (NPs). Recently, the focus on cellular morphology and mechanical behavior is gaining relevance in order [...] Read more.
The side effects induced by nanoparticle exposure at a cellular level are one of the priority research topics due to the steady increase in the use of nanoparticles (NPs). Recently, the focus on cellular morphology and mechanical behavior is gaining relevance in order to fully understand the cytotoxic mechanisms. In this regard, we have evaluated the morphomechanical alteration in human breast adenocarcinoma cell line (MCF-7) exposed to TiO2NPs at two different concentrations (25 and 50 µg/mL) and two time points (24 and 48 h). By using confocal and atomic force microscopy, we demonstrated that TiO2NP exposure induces significant alterations in cellular membrane elasticity, due to actin proteins rearrangement in cytoskeleton, as calculated in correspondence to nuclear and cytoplasmic compartments. In this work, we have emphasized the alteration in mechanical properties of the cellular membrane, induced by nanoparticle exposure. Full article
(This article belongs to the Special Issue Biomechanics of Cell Membrane)
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14 pages, 2005 KiB  
Article
Resveratrol-Induced Temporal Variation in the Mechanical Properties of MCF-7 Breast Cancer Cells Investigated by Atomic Force Microscopy
by Jagoba Iturri, Andreas Weber, Alberto Moreno-Cencerrado, Maria dM Vivanco, Rafael Benítez, Stefano Leporatti and José Luis Toca-Herrera
Int. J. Mol. Sci. 2019, 20(13), 3275; https://doi.org/10.3390/ijms20133275 - 03 Jul 2019
Cited by 22 | Viewed by 3793
Abstract
Atomic force microscopy (AFM) combined with fluorescence microscopy has been used to quantify cytomechanical modifications induced by resveratrol (at a fixed concentration of 50 µM) in a breast cancer cell line (MCF-7) upon temporal variation. Cell indentation methodology has been utilized to determine [...] Read more.
Atomic force microscopy (AFM) combined with fluorescence microscopy has been used to quantify cytomechanical modifications induced by resveratrol (at a fixed concentration of 50 µM) in a breast cancer cell line (MCF-7) upon temporal variation. Cell indentation methodology has been utilized to determine simultaneous variations of Young’s modulus, the maximum adhesion force, and tether formation, thereby determining cell motility and adhesiveness. Effects of treatment were measured at several time-points (0–6 h, 24 h, and 48 h); longer exposures resulted in cell death. Our results demonstrated that AFM can be efficiently used as a diagnostic tool to monitor irreversible morpho/nano-mechanical changes in cancer cells during the early steps of drug treatment. Full article
(This article belongs to the Special Issue Biomechanics of Cell Membrane)
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18 pages, 2647 KiB  
Article
Functional Characterization of Colon Cancer-Associated Mutations in ADAM17: Modifications in the Pro-Domain Interfere with Trafficking and Maturation
by Egor Pavlenko, Anne-Sophie Cabron, Philipp Arnold, Jan Philipp Dobert, Stefan Rose-John and Friederike Zunke
Int. J. Mol. Sci. 2019, 20(9), 2198; https://doi.org/10.3390/ijms20092198 - 04 May 2019
Cited by 10 | Viewed by 3386
Abstract
Colorectal cancer is one of the most commonly diagnosed malignancies in the Western world and is associated with elevated expression and activity of epidermal growth factor receptors (EGF-R). The metalloproteinase ADAM17 is involved in EGF-R activation by processing EGF-R ligands from membrane-bound pro-ligands. [...] Read more.
Colorectal cancer is one of the most commonly diagnosed malignancies in the Western world and is associated with elevated expression and activity of epidermal growth factor receptors (EGF-R). The metalloproteinase ADAM17 is involved in EGF-R activation by processing EGF-R ligands from membrane-bound pro-ligands. Underlining the link between colon cancer and ADAM17, genetic intestinal cancer models in ADAM17-deficient mice show a reduced tumor burden. In this study, we characterize point mutations within the ADAM17 gene found in the tissue of colon cancer patients. In order to shed light on the role of ADAM17 in cancer development, as well as into the mechanisms that regulate maturation and cellular trafficking of ADAM17, we here perform overexpression studies of four ADAM17 variants located in the pro-, membrane-proximal- and cytoplasmic-domain of the ADAM17 protein in ADAM10/17-deficient HEK cells. Interestingly, we found a cancer-associated point mutation within the pro-domain of ADAM17 (R177C) to be most impaired in its proteolytic activity and trafficking to the cell membrane. By comparing this variant to an ADAM17 construct lacking the entire pro-domain, we discovered similar functional limitations and propose a crucial role of the pro-domain for ADAM17 maturation, cellular trafficking and thus proteolytic activity. Full article
(This article belongs to the Special Issue Biomechanics of Cell Membrane)
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