Mechano-sensing by actin filaments and focal adhesion proteins

Mechanosensitive ion channels have long been the only established molecular class of cell mechanosensors with known molecular entities. However, recent advances in the state-of-the-art techniques, including single-molecule manipulation and imaging, have enabled an investigation of non-channel type cell mechanosensors and the underlying biophysical mechanisms of their activation. To date, two focal adhesion proteins, talin and p130Cas, have been postulated to act as putative mechanosensors, acting through mechano-induced unfolding of their particular soft domain(s) susceptible to phosphorylation. More recently, the actin filament has been demonstrated to act as a mechanosensor in the presence of the soluble actin-severing protein, cofilin. The cofilin severing activity negatively depends on the tension in the actin filament through tension-dependent binding/unbinding of cofilin to/from the actin filament. As a result, relaxed actin filaments are severed, while tensed ones are either not severed or severed after a long delay. Here we review the latest progress in the mechanosensing by non-channel type proteins and discuss the possible physiological roles of the mechanosensing performed by actin filaments in the course of cell migration.