Dynein Harnesses Active Fluctuations of Microtubules for Faster Movement

The cytoskeleton forms a dynamic network that generates fluctuations larger than thermal agitation of the cytoplasm¹. Here, we tested whether dynein, a minus-end-directed microtubule (MT) motor², can harness energy from these fluctuations using optical trapping in vitro. We show that dynein forms an asymmetric slip bond with MTs, where its detachment rate increases more slowly under hindering forces than assisting forces. This asymmetry enables dynein to generate unidirectional motility towards the minus-end from force fluctuations. Consistent with our model, oscillatory forces exerted by the trap drive dynein stepping without net force and ATP. Dynein is capable of ratcheting towards the minus-end even when the net force is in the plus-end direction. With ATP, force oscillations increase the velocity and stall force of dynein as it transports cargos and glides MTs. Therefore, dynein is a mechanical ratchet that rectifies cytoskeletal fluctuations to move faster and resists higher forces along MTs.