Figure 6.

Mechanical loss-of-function (mLOF) to study tethered proteins. a A generic force-bearing, mechanosensing protein containing both exposed (1) and cryptic (2) signaling sites. The activity of site 2 is force dependent since mechanical load induces its exposure via domain unfolding. b Traditional KO/KD systems get rid of the targeted protein, which interferes both with its mechanical and non-mechanical functions (alterations compared to wild-type are indicated in bold type at the bottom). In contrast, mLOF probes protein mechanical functions specifically by cleaving the protein and locking it in a low-force mechanosensing state.