Binding of ZO-1 to alpha 5 beta 1 integrins regulates the mechanical properties of alpha 5 beta 1-fibronectin links

摘要

Fundamental processes in cell adhesion, motility, and rigidity adaptation are regulated by integrin-mediated adhesion to the extracellular matrix (ECM). The link between the ECM component fibronectin (fn) and integrin alpha 5 beta 1 forms a complex with ZO-1 in cells at the edge of migrating monolayers, regulating cell migration. However, how this complex affects the alpha 5 beta 1-fn link is unknown. Here we show that the alpha 5 beta 1/ZO-1 complex decreases the resistance to force of alpha 5 beta 1-fn adhesions located at the edge of migrating cell monolayers while also increasing alpha 5 beta 1 recruitment. Consistently with a molecular clutch model of adhesion, this effect of ZO-1 leads to a decrease in the density and intensity of adhesions in cells at the edge of migrating monolayers. Taken together, our results unveil a new mode of integrin regulation through modification of the mechanical properties of integrin-ECM links, which may be harnessed by cells to control adhesion and migration.