title: Mechanically activated integrin switch controls alpha5beta1 function.
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(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.
authors.affiliation: Institute for Medicine and Engineering, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Julie C
authors.initials: JC
authors.lastname: Friedland
authors.forename: Mark H
authors.initials: MH
authors.lastname: Lee
authors.forename: David
authors.initials: D
authors.lastname: Boettiger
mesh_terms: D000199:Actins; D055592:Biophysical Phenomena; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D003599:Cytoskeleton / Q000502:physiology*; D005353:Fibronectins / Q000737:chemistry / Q000378:metabolism*; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D006801:Humans; D039081:Integrin alpha5beta1 / Q000737:chemistry* / Q000378:metabolism*; D008024:Ligands; D008958:Models, Molecular; D024462:Myosin Type II / Q000037:antagonists & inhibitors / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D011487:Protein Conformation; D015398:Signal Transduction
chemical_list: D000199:Actins; D005353:Fibronectins; D039081:Integrin alpha5beta1; D008024:Ligands; D051416:Focal Adhesion Protein-Tyrosine Kinases; D024462:Myosin Type II