Actin flow-dependent and -independent force transmission through integrins

Significance The current paradigm for force transmission between cells and the extracellular matrix is the focal adhesion clutch, in which highly dynamic bonds involving the cytoskeletal linker proteins talin and vinculin transmit tension between moving actin filaments and immobile integrins. We found, however, that while dynamic bonds dominate at cell edges where actin flow is rapid, force transfer in adhesions further from the edge that may be linked to actin bundles is transmitted mainly through more stable interactions. Vinculin contributes to stable and not dynamic bonds as previously thought. We identify the protein interactions that mediate these mechanisms and demonstrate modulation by matrix stiffness. These data therefore substantially revise our view of force transmission in cell-matrix adhesions.