Cell-to-cell junctions are crucial mechanical and signaling hubs that connect cells within tissues and probe the mechanics of the surrounding environment. Although the capacity of cell-to-extracellular-matrix (ECM) adhesions to sense matrix mechanics and proportionally modify cell functions is well established, cell-cell adhesions only recently emerged as a new class of force sensors. This finding exposes new pathways through which force can instruct cell functions. This review highlights recent findings, which demonstrate that protein complexes associated with classical cadherins, the principal architectural proteins at cell-cell junctions in all soft tissues, are mechanosensors. We further discuss the current understanding of the rudiments of a cadherin-based mechanosensing and transduction pathway, which is distinct from the force sensing machinery of cell-ECM adhesions.

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