Mechanically activated integrin switch controls alpha5beta1 function

Science. 2009 Jan 30;323(5914):642-4. doi: 10.1126/science.1168441.


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(5)beta(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 directly controls the alpha(5)beta(1)-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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Actins
  • Biophysical Phenomena
  • Cell Adhesion
  • Cell Line, Tumor
  • Cytoskeleton / physiology*
  • Fibronectins / chemistry
  • Fibronectins / metabolism*
  • Focal Adhesion Protein-Tyrosine Kinases / metabolism
  • Humans
  • Integrin alpha5beta1 / chemistry*
  • Integrin alpha5beta1 / metabolism*
  • Ligands
  • Models, Molecular
  • Myosin Type II / antagonists & inhibitors
  • Myosin Type II / metabolism
  • Phosphorylation
  • Protein Binding
  • Protein Conformation
  • Signal Transduction


  • Actins
  • Fibronectins
  • Integrin alpha5beta1
  • Ligands
  • Focal Adhesion Protein-Tyrosine Kinases
  • Myosin Type II