Proc. Natl Acad. Sci. USA (2013)

Treading a one-dimensional path might sound easy, but the mechanics of getting from A to B in a cell are far from straightforward. Michael Hinczewski and colleagues have developed an analytical model capable of fully characterizing the complex dynamics of myosin V, one of the motor proteins tasked with transporting cargo along biopolymer filaments.

The protein comprises two filament-binding heads connected by a pair of lever arms. As the motor trades chemical energy for mechanical output, the conformations of these arms are modified, effecting a hand-over-hand dynamics as the heads detach and rebind to move along polar biopolymers. Large loads oppose the forward bias, increasing the likelihood of the motor stepping backwards, and giving rise to the 'foot stomping' behaviour seen in single-molecule studies — whereby one of the heads detaches from the filament, only to reattach moments later to the very same site.

Hinczewski et al. encoded the polymeric nature of the lever arms in their theory and solved the associated first-passage problem, examining the effects of a backward load, forward bias and preferential binding. The theory reproduces experimental data, suggests that the mechanism is robust to variation in motor design and predicts the load dependence of the foot-stomping dynamics.