Abstract
SignificanceTalin is a mechanosensitive adaptor protein that links integrins to the actin cytoskeleton at cell-extracellular matrix adhesions. Although the C-terminal actin-binding domain ABS3 of talin is required for function, it binds weakly to actin in solution. We show that ABS3 binds actin strongly only when subjected to mechanical forces comparable to those generated by the cytoskeleton. Moreover, the interaction between ABS3 and actin depends strongly on the direction of force in a manner predicted to organize actin to facilitate adhesion growth and efficient cytoskeletal force generation. These characteristics can explain how force sensing by talin helps to nucleate adhesions precisely when and where they are required to transmit force between the cytoskeleton and the extracellular matrix.