Single-cell response to stiffness exhibits muscle-like behavior
Edited by Tom C. Lubensky, University of Pennsylvania, Philadelphia, PA, and approved August 14, 2009
Abstract
Living cells sense the rigidity of their environment and adapt their activity to it. In particular, cells cultured on elastic substrates align their shape and their traction forces along the direction of highest stiffness and preferably migrate towards stiffer regions. Although numerous studies investigated the role of adhesion complexes in rigidity sensing, less is known about the specific contribution of acto-myosin based contractility. Here we used a custom-made single-cell technique to measure the traction force as well as the speed of shortening of isolated myoblasts deflecting microplates of variable stiffness. The rate of force generation increased with increasing stiffness and followed a Hill force–velocity relationship. Hence, cell response to stiffness was similar to muscle adaptation to load, reflecting the force-dependent kinetics of myosin binding to actin. These results reveal an unexpected mechanism of rigidity sensing, whereby the contractile acto-myosin units themselves can act as sensors. This mechanism may translate anisotropy in substrate rigidity into anisotropy in cytoskeletal tension, and could thus coordinate local activity of adhesion complexes and guide cell migration along rigidity gradients.
Acknowledgments.
We thank Sophie Asnacios, Nicolas Biais, Jean-Pierre Henry and Sandra Lerouge for critical reading of the manuscript and precious advice. We thank all members of the team “Physique du Vivant” for many helpful discussions. This work was supported by grants from the Ministère de la Recherche (ACI Jeune chercheur), from the Centre National de la Recherche Scientifique (Physique et Chimie du Vivant), from the Paris-Diderot (Paris 7) University (Bonus Qualité Recherche), and from the Association pour la Recherche sur le Cancer (subvention libre” #3115). B.F. was supported by funding from Deutsche Forschungsgemeinschaft, and A.G. was supported by a Région Ile de France doctoral fellowship. Physique du Vivant is a member of the GDR 3070 CellTiss of the Centre National de la Recherche Scientifique.
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© 2009.
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Received: April 17, 2009
Published online: October 27, 2009
Published in issue: October 27, 2009
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Acknowledgments
We thank Sophie Asnacios, Nicolas Biais, Jean-Pierre Henry and Sandra Lerouge for critical reading of the manuscript and precious advice. We thank all members of the team “Physique du Vivant” for many helpful discussions. This work was supported by grants from the Ministère de la Recherche (ACI Jeune chercheur), from the Centre National de la Recherche Scientifique (Physique et Chimie du Vivant), from the Paris-Diderot (Paris 7) University (Bonus Qualité Recherche), and from the Association pour la Recherche sur le Cancer (subvention libre” #3115). B.F. was supported by funding from Deutsche Forschungsgemeinschaft, and A.G. was supported by a Région Ile de France doctoral fellowship. Physique du Vivant is a member of the GDR 3070 CellTiss of the Centre National de la Recherche Scientifique.
Notes
This article is a PNAS Direct Submission.
This article contains supporting information online at www.pnas.org/cgi/content/full/0903994106/DCSupplemental.
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The authors declare no conflict of interest.
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Single-cell response to stiffness exhibits muscle-like behavior, Proc. Natl. Acad. Sci. U.S.A.
106 (43) 18243-18248,
https://doi.org/10.1073/pnas.0903994106
(2009).
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