Two-piconewton slip bond between fibronectin and the cytoskeleton depends on talin

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Abstract
Mechanical forces on matrix–integrin–cytoskeleton linkages are crucial for cell viability, morphology and organ function1. The production of force depends on the molecular connections from extracellular-matrix–integrin complexes to the cytoskeleton2,3. The minimal matrix complex causing integrin–cytoskeleton connections is a trimer of fibronectin's integrin-binding domain FNIII7-10 (ref. 4). Here we report a specific, molecular slip bond that was broken repeatedly by a force of 2 pN at the cellular loading rate of 60 nm s-1; this occurred with single trimer beads but not with monomer. Talin1, which binds to both integrins and actin filaments in vitro, is required for the 2-pN slip bond and rapid cytoskeleton binding. Further, inhibition of fibronectin binding to αvβ3 and deletion of β3 markedly decreases the 2-pN force peak. We suggest that talin1 initially forms a molecular slip bond between closely packed fibronectin–integrin complexes and the actin cytoskeleton, which can apply a low level of force to fibronectin until many bonds form or a signal is received to activate a force response.