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

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.

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Figure 1: A discrete fibronectin trimer–αvβ3 integrin linkage was broken by 2 pN.
Figure 2: The 2-pN force peak requires talin1.
Figure 3: The 2-pN force peak was observed in three different cell lines.

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Acknowledgements

We thank H. Erickson for FNIII7-10 monomer and trimer constructs; A. J. Woods for the talin1-ABS construct; R. Hynes for β3 cell lines; J. Sap for RPTPα cell lines; G. von Wichert and N. Heckenberg for discussions; and all the Sheetz laboratory members for consistent help. This work was supported by a grant from the NIH to M.P.S. Work in D.R.C.'s laboratory was funded by the Wellcome Trust.

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Correspondence to Michael P. Sheetz.

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Jiang, G., Giannone, G., Critchley, D. et al. Two-piconewton slip bond between fibronectin and the cytoskeleton depends on talin. Nature 424, 334–337 (2003). https://doi.org/10.1038/nature01805

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