title: Nascent Integrin Adhesions Form on All Matrix Rigidities after Integrin Activation.
abstract: Integrin adhesions assemble and mature in response to ligand binding and mechanical factors, but the molecular-level organization is not known. We report that ∼100-nm clusters of ∼50 β3-activated integrins form very early adhesions under a wide variety of conditions on RGD surfaces. These adhesions form similarly on fluid and rigid substrates, but most adhesions are transient on rigid substrates. Without talin or actin polymerization, few early adhesions form, but expression of either the talin head or rod domain in talin-depleted cells restores early adhesion formation. Mutation of the integrin binding site in the talin rod decreases cluster size. We suggest that the integrin clusters constitute universal early adhesions and that they are the modular units of cell matrix adhesions. They require the association of activated integrins with cytoplasmic proteins, in particular talin and actin, and cytoskeletal contraction on them causes adhesion maturation for cell motility and growth.
authors.affiliation: Mechanobiology Institute, National University of Singapore, Singapore 117411.
authors.forename: Rishita
authors.initials: R
authors.lastname: Changede
authors.affiliation: Mechanobiology Institute, National University of Singapore, Singapore 117411.
authors.forename: Xiaochun
authors.initials: X
authors.lastname: Xu
authors.affiliation: Mechanobiology Institute, National University of Singapore, Singapore 117411.
authors.forename: Felix
authors.initials: F
authors.lastname: Margadant
authors.affiliation: Mechanobiology Institute, National University of Singapore, Singapore 117411; Department of Biological Sciences, Columbia University, New York, NY 10027, USA. Electronic address: ms2001@columbia.edu.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Sheetz
mesh_terms: D000199:Actins / Q000378:metabolism; D000465:Algorithms; D000818:Animals; D001665:Binding Sites; D002448:Cell Adhesion; D002465:Cell Movement; D003593:Cytoplasm / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D039661:Integrin beta3 / Q000378:metabolism*; D008024:Ligands; D051379:Mice; D009154:Mutation; D009842:Oligopeptides / Q000378:metabolism*; D011485:Protein Binding; D013314:Stress, Mechanical; D016608:Talin / Q000378:metabolism*
chemical_list: D000199:Actins; D039661:Integrin beta3; D008024:Ligands; D009842:Oligopeptides; D016608:Talin; D049452:Green Fluorescent Proteins; C047981:arginyl-glycyl-aspartic acid