α-Catenin links integrin adhesions to F-actin to regulate ECM mechanosensing and rigidity dependence

Abstract

Both cell–cell and cell–matrix adhesions are regulated by mechanical signals, but the mechanobiological processes that mediate the cross talk between these structures are poorly understood. Here we show that α-catenin, a mechanosensitive protein that is classically linked with cadherin-based adhesions, associates with and regulates integrin adhesions. α-Catenin is recruited to the edges of mesenchymal cells, where it interacts with F-actin. This is followed by mutual retrograde flow of α-catenin and F-actin from the cell edge, during which α-catenin interacts with vinculin within integrin adhesions. This interaction affects adhesion maturation, stress-fiber assembly, and force transmission to the matrix. In epithelial cells, α-catenin is present in cell–cell adhesions and absent from cell–matrix adhesions. However, when these cells undergo epithelial-to-mesenchymal transition, α-catenin transitions to the cell edge, where it facilitates proper mechanosensing. This is highlighted by the ability of α-catenin–depleted cells to grow on soft matrices. These results suggest a dual role of α-catenin in mechanosensing, through both cell–cell and cell–matrix adhesions.