Towards a Dynamic Understanding of Cadherin-Based Mechanobiology

Cadherin-based cell–cell adhesions are a primary determinant of tissue structure. For several decades, it had been thought that the primary function of these ubiquitous structures was to resist external mechanical loads. Here we review recent evidence that cadherins also couple together the force-generating actomyosin cytoskeletons of neighbouring cells, serve as potent regulators of the actomyosin cytoskeleton, and activate diverse signalling pathways in response to applied load. In considering the force sensitivity of the molecular-scale processes that mediate these events, we propose a dynamic picture of the force-sensitive processes in cell–cell contacts. This quantitative and physical understanding of the mechanobiology of cadherin cell–cell junctions will aid endeavours to study the fundamental processes mediating the development and maintenance of tissue structure.

TrendsCadherin complexes bear mechanical forces that arise from cellular contractility in adherent cells. Coupling to actomyosin via association with myosin-bound F-actin leads to contractile forces being applied to cadherins and their associated proteins.Bond properties within the cadherin–catenin complex influence mechanosensitivity of cadherin junctions. Catch bonds have been identified to mediate adhesive binding between cadherin ectodomains and the association of the cadherin–catenin complex with F-actin.Functional responses to mechanical stimulation of cadherin adhesions are diverse and operate over substantially different time scales. These include changes in actin dynamics (operating over minutes) and entry into the cell cycle (operating over hours).