Evidence of a large-scale mechanosensing mechanism for cellular adaptation to substrate stiffness
Léa Trichet,Jimmy Le Digabel,Rhoda J. Hawkins,Sri Ram Krishna Vedula,Mukund Gupta,Claire Ribrault,Pascal Hersen,Raphaël Voituriez,Benoit Ladoux +8 more
TLDR
It is shown that large-scale mechanosensing leads to an adaptative response of cell migration to stiffness gradients, and not only that cells migrate preferentially toward stiffer substrates, but also that this response is optimal in a narrow range of rigidities.Abstract:
Cell migration plays a major role in many fundamental biological processes, such as morphogenesis, tumor metastasis, and wound healing. As they anchor and pull on their surroundings, adhering cells actively probe the stiffness of their environment. Current understanding is that traction forces exerted by cells arise mainly at mechanotransduction sites, called focal adhesions, whose size seems to be correlated to the force exerted by cells on their underlying substrate, at least during their initial stages. In fact, our data show by direct measurements that the buildup of traction forces is faster for larger substrate stiffness, and that the stress measured at adhesion sites depends on substrate rigidity. Our results, backed by a phenomenological model based on active gel theory, suggest that rigidity-sensing is mediated by a large-scale mechanism originating in the cytoskeleton instead of a local one. We show that large-scale mechanosensing leads to an adaptative response of cell migration to stiffness gradients. In response to a step boundary in rigidity, we observe not only that cells migrate preferentially toward stiffer substrates, but also that this response is optimal in a narrow range of rigidities. Taken together, these findings lead to unique insights into the regulation of cell response to external mechanical cues and provide evidence for a cytoskeleton-based rigidity-sensing mechanism.read more
Citations
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Mechanotransduction and extracellular matrix homeostasis
TL;DR: Progress towards understanding the molecular, cellular and tissue-level effects that promote mechanical homeostasis has helped to identify key questions for future research.
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Mechanical forces direct stem cell behaviour in development and regeneration
Kyle H. Vining,David J. Mooney +1 more
TL;DR: Fundamental insights into the mechanobiology of stem cells also inform the design of artificial niches to support stem cells for regenerative therapies.
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Physical influences of the extracellular environment on cell migration
Guillaume Charras,Erik Sahai +1 more
TL;DR: The findings that have emerged from approaches that span these disciplines are outlined, with a focus on actin-based cell migration in environments with different stiffness, dimensionality and geometry.
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Force-dependent conformational switch of α-catenin controls vinculin binding.
Mingxi Yao,Wu Qiu,Ruchuan Liu,Artem K. Efremov,Peiwen Cong,Rima Seddiki,Manon Payre,Chwee Teck Lim,Benoit Ladoux,René-Marc Mège,Jie Yan +10 more
TL;DR: It is demonstrated that physiologically relevant forces reversibly unfurl α-catenin, activating vinculin binding, which then stabilizes α-Catenin in its open conformation, transforming force into a sustainable biochemical signal.
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Measuring cell-generated forces: a guide to the available tools
TL;DR: This review of established methods to measure forces generated by cells highlights the technical challenges associated with implementing each technique in a biological laboratory and introduces the established methods.
References
More filters
Journal ArticleDOI
Matrix elasticity directs stem cell lineage specification.
TL;DR: Naive mesenchymal stem cells are shown here to specify lineage and commit to phenotypes with extreme sensitivity to tissue-level elasticity, consistent with the elasticity-insensitive commitment of differentiated cell types.
Journal ArticleDOI
Tissue Cells Feel and Respond to the Stiffness of Their Substrate
TL;DR: An understanding of how tissue cells—including fibroblasts, myocytes, neurons, and other cell types—sense matrix stiffness is just emerging with quantitative studies of cells adhering to gels with which elasticity can be tuned to approximate that of tissues.
Journal ArticleDOI
Tensional homeostasis and the malignant phenotype.
Matthew J. Paszek,Nastaran Zahir,Kandice R. Johnson,Johnathon N. Lakins,Gabriela I. Rozenberg,Amit Gefen,Cynthia A. Reinhart-King,Susan S. Margulies,Micah Dembo,David Boettiger,Daniel A. Hammer,Valerie M. Weaver +11 more
TL;DR: It is found that tumors are rigid because they have a stiff stroma and elevated Rho-dependent cytoskeletal tension that drives focal adhesions, disrupts adherens junctions, perturbs tissue polarity, enhances growth, and hinders lumen formation.
Journal ArticleDOI
Cell Movement Is Guided by the Rigidity of the Substrate
TL;DR: It is discovered that changes in tissue rigidity and strain could play an important controlling role in a number of normal and pathological processes involving cell locomotion, including morphogenesis, the immune response, and wound healing.
Journal ArticleDOI
Cell locomotion and focal adhesions are regulated by substrate flexibility
Robert J. Pelham,Yu-li Wang +1 more
TL;DR: The ability of cells to survey the mechanical properties of their surrounding environment is demonstrated and the possible involvement of both protein tyrosine phosphorylation and myosin-generated cortical forces in this process is suggested.