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Abstract

Cells sense the environment's mechanical stiffness to control their own shape, migration, and fate. To better understand stiffness sensing, we constructed a stochastic model of the “motor-clutch” force transmission system, where molecular clutches link F-actin to the substrate and mechanically resist myosin-driven F-actin retrograde flow. The model predicts two distinct regimes: (i) “frictional slippage,” with fast retrograde flow and low traction forces on stiff substrates and (ii) oscillatory “load-and-fail” dynamics, with slower retrograde flow and higher traction forces on soft substrates. We experimentally confirmed these model predictions in embryonic chick forebrain neurons by measuring the nanoscale dynamics of single–growth-cone filopodia. Furthermore, we experimentally observed a model-predicted switch in F-actin dynamics around an elastic modulus of 1 kilopascal. Thus, a motor-clutch system inherently senses and responds to the mechanical stiffness of the local environment.

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This research was supported by the Institute for Engineering in Medicine at the University of Minnesota, NSF (grant MCB-0615568), and the National Institute of General Medical Sciences (grant R01-GM-76177). We thank P. Letourneau, D. Bray, and E. Tuzel for stimulating discussions; N. Simha for helpful discussions on gel mechanics; N. Koyano for assistance with in ovo electroporation; and members of the Odde Lab, D. Seetapun, A. Bicek, M. Gardner, and T. Dahl for technical assistance.

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Published In

Science
Volume 322 | Issue 5908
12 December 2008

Submission history

Received: 22 July 2008
Accepted: 29 October 2008
Published in print: 12 December 2008

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Notes

Supporting Online Material
www.sciencemag.org/cgi/content/full/322/5908/1687/DC1
Materials and Methods
SOM Text
Figs. S1 to S12
Table S1
References
Movies S1 to S5

Authors

Affiliations

Clarence E. Chan
Department of Biomedical Engineering, University of Minnesota, Minneapolis, MN 55455, USA.
David J. Odde* [email protected]
Department of Biomedical Engineering, University of Minnesota, Minneapolis, MN 55455, USA.

Notes

*
To whom correspondence should be addressed. E-mail: [email protected]

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