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Science 323 (5914): 642-644

Copyright © 2009 by the American Association for the Advancement of Science

Mechanically Activated Integrin Switch Controls {alpha}5β1 Function

Julie C. Friedland,1,2* Mark H. Lee,1,2* David Boettiger1,2,3{dagger}

Abstract: The cytoskeleton, integrin-mediated adhesion, and substrate stiffness control a common set of cell functions required for development and homeostasis that are often deranged in cancer. The connection between these mechanical elements and chemical signaling processes is not known. Here, we show that {alpha}5β1 integrin switches between relaxed and tensioned states in response to myosin II–generated cytoskeletal force. Force combines with extracellular matrix stiffness to generate tension that triggers the integrin switch. This switch directly controls the {alpha}5β1-fibronectin bond strength through engaging the synergy site in fibronectin and is required to generate signals through phosphorylation of focal adhesion kinase. In the context of tissues, this integrin switch connects cytoskeleton and extracellular matrix mechanics to adhesion-dependent motility and signaling pathways.

1 Institute for Medicine and Engineering, University of Pennsylvania, Philadelphia, PA 19104, USA.
2 Department of Microbiology, University of Pennsylvania, Philadelphia, PA 19104, USA.
3 Department of Pharmacology, University of Pennsylvania, Philadelphia, PA 19104, USA.

* These authors contributed equally to the work.

{dagger} To whom correspondence should be addressed: E-mail: boettige{at}upenn.edu

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