Switching of myosin-V motion between the lever-arm swing and Brownian search-and-catch

Motor proteins are force-generating nanomachines that are highly adaptable to their ever-changing biological environments and have a high energy conversion efficiency. Here we constructed an imaging system that uses optical tweezers and a DNA handle to visualize elementary mechanical processes of a nanomachine under load. We apply our system to myosin-V, a well-known motor protein that takes 72 nm 'hand-over-hand' steps composed of a 'lever-arm swing' and a 'Brownian search-and-catch'. We find that the lever-arm swing generates a large proportion of the force at low load (<0.5 pN), resulting in 3 kBT of work. At high load (1.9 pN), however, the contribution of the Brownian search-and-catch increases to dominate, reaching 13 kBT of work. We believe the ability to switch between these two force-generation modes facilitates myosin-V function at high efficiency while operating in a dynamic intracellular environment. The motor protein myosin-V transports cargo along actin filaments, but the biophysical mechanisms by which myosin-V generates force are unclear. Here, optical tweezers and a DNA handle are used to study the forces generated by myosin-V: the mechanism of force generation is found to depend on the load applied.