Biophysics of actin filament severing by cofilin

The continuous assembly and disassembly of actin filament networks is vital for cellular processes including division, growth, and motility. Network remodeling is facilitated by cofilins, a family of essential regulatory proteins that fragment actin filaments. Cofilin induces net structural changes in filaments that render them more compliant in bending and twisting. A model in which local stress accumulation at mechanical discontinuities, such as boundaries of bare and cofilin-decorated filament segments, accounts for the cofilin concentration dependence of severing, including maximal activity at sub-stoichiometric binding densities. Real-time imaging of cofilin-mediated filament severing supports the boundary-fracture model. The severing model predicts that fragmentation is promoted by factors modulating filament mechanics (e.g. tethering, cross-linking, or deformation), possibly explaining enhanced in vivo severing activities.