Focal adhesions as mechanosensors: A physical mechanism

Focal adhesions (FA) are large, multiprotein complexes that provide a mechanical link between the cytoskeletal contractile machinery and the extracellular matrix. FA exhibit mechanosensitive properties; they self-assemble and elongate upon application of pulling forces and dissociate when these forces are decreased. We propose a thermodynamic model for the mechanosensitivity of FA, according to which a molecular aggregate, subjected to pulling forces, tends to grow in the direction of force application by incorporating additional molecules. We demonstrate that this principle is consistent with the phenomenology of FA dynamics by considering a one-dimensional protein aggregate subjected to pulling forces and anchored to the substrate. Depending on the force level, force distribution along the aggregate, and the character of its anchoring to the substrate, the aggregate is predicted to exhibit distinct modes of assembly that are largely consistent with the experimentally observed FA behavior. We define here specific conditions that can lead to the different regimes of FA assembly, including growth, steady state, and disassembly.