Clustering of α5β1 integrins determines adhesion strength whereas αvβ3 and talin enable mechanotransduction

Pere Roca-Cusachs, Nils C. Gauthier, Armando Del Rio, Michael Sheetz

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Abstract

A key molecular link between cells and the extracellular matrix is the binding between fibronectin and integrins α5β1 and αvβ3. However, the roles of these different integrins in establishing adhesion remain unclear. We tested the adhesion strength of fibronectin-integrin-cytoskeleton linkages by applying physiological nanonewton forces to fibronectin-coated magnetic beads bound to cells. We report that the clustering of fibronectin domains within 40 nm led to integrin α5β1 recruitment, and increased the ability to sustain force by over six-fold. This force was supported by α 5β1 integrin clusters. Importantly, we did not detect a role of either integrin αvβ3 or talin 1 or 2 in maintaining adhesion strength. Instead, these molecules enabled the connection to the cytoskeleton and reinforcement in response to an applied force. Thus, high matrix forces are primarily supported by clustered α5β1 integrins, while less stable links to αvβ3 integrins initiate mechanotransduction, resulting in reinforcement of integrin-cytoskeleton linkages through talin-dependent bonds.

Original languageEnglish (US)
Pages (from-to)16245-16250
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume106
Issue number38
DOIs
StatePublished - Sep 22 2009
Externally publishedYes

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