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Mechanically Activated Integrin Switch
Controls alpha-5 beta-1 Function
Julie C. Friedland, Mark H. Lee and David Boettiger.
(2009) Science, in Press.
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 ?5?1 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
controls directly the ?5?1-
fibronectin bond strength through engaging the synergy
site in fibronectin and is
required to generate signals through phosphorylation of
FAK. In the context of
tissues, this integrin switch connects cytoskeleton and
extracellular matrix
mechanics to adhesion dependent motility and signaling
pathways. |
