Structural Biophysics of Cytoskeletal Force Transduction

Cells mechanically interface with their surroundings through the actin cytoskeleton, a network of dynamic actin filaments, force-generating myosin motor proteins, and hundreds of associated binding proteins. The cytoskeleton plays a central role in the capacity of cells to sense and respond to physical forces and the mechanical properties of their environments (mechanosensing). Mechanosensing is essential for development and tissue homeostasis, and it is frequently disrupted in hereditary developmental disorders and cancers. Mechanistic studies of cytoskeletal mechanosensing have uncovered mechanically regulated binding interactions between cytoskeletal proteins, as well as force-sensitive dynamics of subcellular cytoskeletal networks that emerge at the scale of hundreds to thousands of molecules. Here, we review recent efforts to decipher the biophysical and protein structural bases of cytoskeletal mechanosensing, emphasizing emerging approaches for directly visualizing active force transduction from the angstrom to micrometer scale.