Dynamics of Mechanosensitive Nascent Adhesion Formation.

Cellular migration is a tightly regulated process that involves actin cytoskeleton, adaptor proteins, and integrin receptors. Forces are transmitted extracellularly through protein complexes of these molecules, called adhesions. Adhesions anchor the cell to its substrate, allowing it to migrate. In Chinese hamster ovary cells, three classes of adhesion can be identified: nascent adhesions (NAs), focal complexes, and focal adhesions, ranked here ascendingly based on size and stability. To understand the dynamics and mechanosensitive properties of NAs, a biophysical model of these NAs as colocalized clusters of integrins and adaptor proteins is developed. The model is then analyzed to characterize the dependence of NA area on biophysical parameters that regulate the number of integrins and adaptor proteins within NAs through a mechanosensitive coaggregation mechanism. Our results reveal that NA formation is triggered beyond a threshold of adaptor protein, integrin, or extracellular ligand densities, with these three factors listed in descending order of their relative influence on NA area. Further analysis of the model also reveals that an increase in coaggregation or reductions in integrin mobility inside the adhesion potentiate NA formation. By extending the model to consider the mechanosensitivity of the integrin bond, we identify mechanical stress, rather than mechanical load, as a permissive mechanical parameter that allows for noise-dependent and independent NA assembly, despite both parameters producing a bistable switch possessing a hysteresis. Stochastic simulations of the model confirm these results computationally. This study thus provides insight into the mechanical conditions defining NA dynamics.