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Chenling Dong, Xiaofeng Chen, Bin Chen
It is important to learn features of locally applied forces by cells during matrix rigidity sensing, since the function of mechanosensing proteins would be affected by force magnitude, loading velocity, or even loading history. Here, we investigate a rigidity-sensing apparatus consisting of a contractile unit on matrices. Strikingly, our analysis indicates that the matrix rigidity is not only sensed with a fixed step size in displacement but also with a fixed apparent loading velocity. The fixed step size is shown to be correlated with the monomer size of actin filament...
March 13, 2018: Biophysical Journal
Takuya Ohmura, Yukinori Nishigami, Atsushi Taniguchi, Shigenori Nonaka, Junichi Manabe, Takuji Ishikawa, Masatoshi Ichikawa
An important habit of ciliates, namely, their behavioral preference for walls, is revealed through experiments and hydrodynamic simulations. A simple mechanical response of individual ciliary beating (i.e., the beating is stalled by the cilium contacting a wall) can solely determine the sliding motion of the ciliate along the wall and result in a wall-preferring behavior. Considering ciliate ethology, this mechanosensing system is likely an advantage in the single cell's ability to locate nutrition. In other words, ciliates can skillfully use both the sliding motion to feed on a surface and the traveling motion in bulk water to locate new surfaces according to the single "swimming" mission...
March 12, 2018: Proceedings of the National Academy of Sciences of the United States of America
Ming Zhong, Yulia Komarova, Jalees Rehman, Asrar B Malik
No abstract text is available yet for this article.
January 1, 2018: Pulmonary Circulation
Katarzyna Pogoda, Paul A Janmey
Understanding the mechanical behavior of human brain is critical to interpret the role of physical stimuli in both normal and pathological processes that occur in CNS tissue, such as development, inflammation, neurodegeneration, aging, and most common brain tumors. Despite clear evidence that mechanical cues influence both normal and transformed brain tissue activity as well as normal and transformed brain cell behavior, little is known about the links between mechanical signals and their biochemical and medical consequences...
2018: Frontiers in Cellular Neuroscience
Ze Gong, Spencer E Szczesny, Steven R Caliari, Elisabeth E Charrier, Ovijit Chaudhuri, Xuan Cao, Yuan Lin, Robert L Mauck, Paul A Janmey, Jason A Burdick, Vivek B Shenoy
Recent evidence has shown that, in addition to rigidity, the viscous response of the extracellular matrix (ECM) significantly affects the behavior and function of cells. However, the mechanism behind such mechanosensitivity toward viscoelasticity remains unclear. In this study, we systematically examined the dynamics of motor clutches (i.e., focal adhesions) formed between the cell and a viscoelastic substrate using analytical methods and direct Monte Carlo simulation. Interestingly, we observe that, for low ECM rigidity, maximum cell spreading is achieved at an optimal level of viscosity in which the substrate relaxation time falls between the timescale for clutch binding and its characteristic binding lifetime...
March 5, 2018: Proceedings of the National Academy of Sciences of the United States of America
Patrick W Oakes, Tamara C Bidone, Yvonne Beckham, Austin V Skeeters, Guillermina R Ramirez-San Juan, Stephen P Winter, Gregory A Voth, Margaret L Gardel
The ability of adherent cells to sense changes in the mechanical properties of their extracellular environments is critical to numerous aspects of their physiology. It has been well documented that cell attachment and spreading are sensitive to substrate stiffness. Here, we demonstrate that this behavior is actually biphasic, with a transition that occurs around a Young's modulus of ∼7 kPa. Furthermore, we demonstrate that, contrary to established assumptions, this property is independent of myosin II activity...
February 27, 2018: Proceedings of the National Academy of Sciences of the United States of America
Jason A Bleedorn, Troy A Hornberger, Craig A Goodman, Zhengling Hao, Susannah J Sample, Ermias Amene, Mark D Markel, Mary Behan, Peter Muir
Mechanical signals play an integral role in the regulation of bone mass and functional adaptation to bone loading. The osteocyte has long been considered the principle mechanosensory cell type in bone, although recent evidence suggests the sensory nervous system may play a role in mechanosensing. The specific signaling pathways responsible for functional adaptation of the skeleton through modeling and remodeling are not clearly defined. In vitro studies suggest involvement of intracellular signaling through mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt), and mammalian target of rapamycin (mTOR)...
2018: PloS One
Antonios N Gargalionis, Efthimia K Basdra, Athanasios G Papavassiliou
Cancer mechanics have lately emerged as a distinct tumor feature that promotes tumor development, invasion, and metastasis. Tumor mechanosensing involves a mechanical interplay between cancer cells, extracellular matrix, and cells of the surrounding stroma. Mechanoreceptors sense alterations of the extracellular mechanical cues and activate signaling molecules, which mediate oncogenic transcription in favor of cancer initiation, survival, growth, and metastasis. Furthermore, alterations of the matrix rigidity and activation of mechano-induced transcriptional regulators has been strongly associated with resistance to anti-cancer agents...
February 26, 2018: Journal of Cellular Biochemistry
Cole Zmurchok, Dhananjay Bhaskar, Leah Edelstein-Keshet
Regulators of the actin cytoskeleton such Rho GTPases can modulate forces developed in cells by promoting actomyosin contraction. At the same time, through mechanosensing, tension is known to affect the activity of Rho GTPases. What happens when these effects act in concert? Using a minimal model (1 GTPase coupled to a Kelvin-Voigt element), we show that two-way feedback between signaling ("RhoA") and mechanical tension (stretching) leads to a spectrum of cell behaviors, including contracted or relaxed cells, and cells that oscillate between these extremes...
February 23, 2018: Physical Biology
(no author information available yet)
No abstract text is available yet for this article.
February 22, 2018: Journal of Cell Science
Tyler J Kirby, Jan Lammerding
The ability of cells to respond to mechanical forces is critical for numerous biological processes. Emerging evidence indicates that external mechanical forces trigger changes in nuclear envelope structure and composition, chromatin organization and gene expression. However, it remains unclear if these processes originate in the nucleus or are downstream of cytoplasmic signals. Here we discuss recent findings that support a direct role of the nucleus in cellular mechanosensing and highlight novel tools to study nuclear mechanotransduction...
February 21, 2018: Nature Cell Biology
Benjamin R Freedman, Ashley B Rodriguez, Cody D Hillin, Stephanie N Weiss, Biao Han, Lin Han, Louis J Soslowsky
Tendon experiences a variety of multiscale changes to its extracellular matrix during mechanical loading at the fascicle, fibre and fibril levels. For example, tensile loading of tendon increases its stiffness, with organization of collagen fibres, and increases cell strain in the direction of loading. Although applied macroscale strains correlate to cell and nuclear strains in uninjured tendon, the multiscale response during tendon healing remains unknown and may affect cell mechanosensing and response. Therefore, this study evaluated multiscale structure-function mechanisms in response to quasi-static tensile loading in uninjured and healing tendons...
February 2018: Journal of the Royal Society, Interface
Charles Samuel Umbaugh, Adriana Diaz-Quiñones, Manoel Figueiredo Neto, Joseph J Shearer, Marxa L Figueiredo
Laminin receptor (67 LR) is a 67 kDa protein derived from a 37 kDa precursor (37 LR). 37/67 LR is a strong clinical correlate for progression, aggression, and chemotherapeutic relapse of several cancers including breast, prostate, and colon. The ability of 37/67 LR to promote cancer cell aggressiveness is further increased by its ability to transduce physiochemical and mechanosensing signals in endothelial cells and modulate angiogenesis. Recently, it was demonstrated that 37/67 LR modulates the anti-angiogenic potential of the secreted glycoprotein pigment epithelium-derived factor (PEDF)...
January 19, 2018: Oncotarget
Jan Kubanek, Poojan Shukla, Alakananda Das, Stephen A Baccus, Miriam B Goodman
Focused ultrasound has been shown to stimulate excitable cells, but the biophysical mechanisms behind this phenomenon remain poorly understood. To provide additional insight, we devised a behavioralgenetic assay applied to the well-characterized nervous system of C. elegans nematodes. We found that pulsed ultrasound elicits robust reversal behavior in wild-type animals in a pressure-, duration-, and pulse protocol- dependent manner. Responses were preserved in mutants unable to sense thermal fluctuations and absent in mutants lacking neurons required for mechanosensation...
February 20, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Zachary R Gallaher, Oswald Steward
Axons within the peripheral nervous system are capable of regeneration, but full functional recovery is rare. Recent work has shown that conditional deletion of two key signaling inhibitors of the PI3K and Jak/Stat pathways-phosphatase and tensin homolog (PTEN) and suppressor of cytokine signaling-3 (SOCS3), respectively-promotes regeneration of normally non-regenerative central nervous system axons. Moreover, in studies of optic nerve regeneration, co-deletion of both PTEN and SOCS3 has an even greater effect...
February 16, 2018: Experimental Neurology
Fangchao Song, Hao Wang, Karin Sauer, Dacheng Ren
Recently, we reported that the stiffness of poly(dimethylsiloxane) (PDMS) affects the attachment of Pseudomonas aeruginosa , and the morphology and antibiotic susceptibility of attached cells. To further understand how P. aeruginosa responses to material stiffness during attachment, the wild-type P. aeruginosa PAO1 and several isogenic mutants were characterized for their attachment on soft and stiff PDMS. Compared to the wild-type strain, mutation of the oprF gene abolished the differences in attachment, growth, and size of attached cells between soft and stiff PDMS surfaces...
2018: Frontiers in Microbiology
Elias H Barriga, Kristian Franze, Guillaume Charras, Roberto Mayor
Collective cell migration is essential for morphogenesis, tissue remodelling and cancer invasion. In vivo, groups of cells move in an orchestrated way through tissues. This movement involves mechanical as well as molecular interactions between cells and their environment. While the role of molecular signals in collective cell migration is comparatively well understood, how tissue mechanics influence collective cell migration in vivo remains unknown. Here we investigated the importance of mechanical cues in the collective migration of the Xenopus laevis neural crest cells, an embryonic cell population whose migratory behaviour has been likened to cancer invasion...
February 14, 2018: Nature
Yoshie Narui, Marcos Sotomayor
Human hearing relies upon the tip-to-tip interaction of two non-classical cadherins, protocadherin-15 (PCDH15) and cadherin-23 (CDH23). Together, these proteins form a filament called the tip link that connects neighboring stereocilia of mechanosensitive hair cells. As sound waves enter the cochlea, the stereocilia deflect and tension is applied to the tip link opening nearby transduction channels. Disruption of the tip link by loud sound or calcium chelators eliminates transduction currents and illustrates that tip-link integrity is critical for mechanosensing...
February 14, 2018: Biochemistry
Nils C Gauthier, Pere Roca-Cusachs
Integrin-mediated adhesions between cells and the extracellular matrix are fundamental for cell function, and one of their main roles is to sense and respond to mechanical force. Here we discuss the different mechanisms that can confer mechanosensitivity to adhesions. We first address molecular mechanisms mediated by force-induced changes in molecular properties, such as binding dynamics or protein conformation. Then, we discuss recent evidence on how these mechanisms are integrated with cellular and extracellular parameters such as myosin and actin activity, membrane tension, and ECM properties, endowing cells with an exquisite ability to both detect and respond to physical and mechanical cues from their environment...
January 26, 2018: Current Opinion in Cell Biology
Menghua Zhao, Julien Dervaux, Tetsuharu Narita, François Lequeux, Laurent Limat, Matthieu Roché
Gel layers bound to a rigid substrate are used in cell culture to control differentiation and migration and to lower the friction and tailor the wetting of solids. Their thickness, often considered a negligible parameter, affects cell mechanosensing or the shape of sessile droplets. Here, we show that the adjustment of coating thickness provides control over energy dissipation during the spreading of flowing matter on a gel layer. We combine experiments and theory to provide an analytical description of both the statics and the dynamics of the contact line between the gel, the liquid, and the surrounding atmosphere...
February 5, 2018: Proceedings of the National Academy of Sciences of the United States of America
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