Nanomechanics at the extracellular matrix-focal adhesion interface

The mechanical properties of the extracellular matrix (ECM) play a crucial role in regulating fundamental cellular processes, including migration, development, and proliferation. Cells generate pulling forces on the ECM, while simultaneously, focal adhesions experience the mechanical cues transmitted from the ECM. However, the molecular mechanisms that enable cells to sense and adapt to their mechanical environment remain poorly understood. Advances in intracellular and extracellular tension sensors have enabled the quantification of the physiologically relevant forces at play, which trigger conformational changes in the involved proteins that can be tracked with single-molecule in vitro techniques. From early AFM experiments focused on stiff ECM proteins like tenascin and fibronectin to recent magnetic tweezers studies of mechanically labile focal adhesion proteins, such as talin and vinculin, we are progressively elucidating the physicochemical principles underlying force-sensing processes. In this review, we discuss recent advances in the study of the nanomechanics of ECM and focal adhesion proteins, highlighting how molecular-scale mechanics drive complex mechanosensing and mechanotransduction processes at the cellular level.