Integrin-based adhesion complexes link the cytoskeleton to the extracellular matrix (ECM) and are central to the construction of multicellular animal tissues. How biological function emerges from the tens to thousands of proteins present within a single adhesion complex remains unclear. We used fluorescent molecular tension sensors to visualize force transmission by individual integrins in living cells. These measurements revealed an underlying functional modularity in which integrin class controlled adhesion size and ECM ligand specificity, while the number and type of connections between integrins and F-actin determined the force per individual integrin. In addition, we found that most integrins existed in a state of near-mechanical equilibrium, a result not predicted by existing models of cytoskeletal force transduction. A revised model that includes reversible cross-links within the F-actin network can account for this result and suggests one means by which cellular mechanical homeostasis can arise at the molecular level.
Bibliographical noteFunding Information:
We thank K. Rothenberg of the Hoffman laboratory (Duke University) for the vin?/? MEFs, M. Franklin from the Liphardt laboratory (Stanford University) for the U2OS cells, and R. F?ssler (Max Planck Institute, Martinsried) for the pKO cells. We thank the Khosla laboratory for their protein purification expertise and access to their equipment. We would also like to thank A. LaCroix from the Hoffman laboratory (Duke University) for useful discussions on FRET-force calibrations and B. Zhong, E. Korkmazhan, C. Garzon-Coral, W. Weis, and O. Chaudhuri for useful discussions and feedback. The data reported in this paper are further detailed in the Supplementary Materials. Research reported in this publication was supported by grants R01-CA172986 and U54-CA210190 to D.J.O. and R01-GM112998-01 and R35-GM130332 to A.R.D. from the National Institutes of Health (NIH). The research of A.R.D. was supported, in part, by a Faculty Scholar from the Howard Hughes Medical Institute. S.J.T. was supported by the John Stauffer Stanford Graduate Fellowship from Stanford, and A.C.C., C.M.M., and L.S.P. were supported by Graduate Research Fellowships from the National Science Foundation (00039202). The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official views of the NIH.
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