@article {Mitra536250, author = {A. Mitra and M. Su{\~n}{\'e} and S. Diez and J. M. Sancho and D. Oriola and J. Casademunt}, title = {A Brownian ratchet model explains the biased sidestepping movement of single-headed kinesin-3 KIF1A}, elocation-id = {536250}, year = {2019}, doi = {10.1101/536250}, publisher = {Cold Spring Harbor Laboratory}, abstract = {The kinesin-3 motor KIF1A is involved in long-ranged axonal transport in neurons. In order to ensure vesicular delivery, motors need to navigate the microtubule lattice and overcome possible roadblocks along the way. The single-headed form of KIF1A is a highly diffusive motor that has been shown to be a prototype of Brownian motor by virtue of a weakly-bound diffusive state to the microtubule. Recently, groups of single-headed KIF1A motors were found to be able to sidestep along the microtubule lattice, creating left-handed helical membrane tubes when pulling on giant unilamellar vesicles in vitro. A possible hypothesis is that the diffusive state enables the motor to explore the microtubule lattice and switch protofilaments, leading to a left-handed helical motion. Here we study microtubule rotation driven by single-headed KIF1A motors using fluorescene-interference contrast (FLIC) microscopy. We find an average rotational pitch of ≃ 1.4 μm which is remarkably robust to changes in the gliding velocity, ATP concentration and motor density. Our experimental results are compared to stochastic simulations of Brownian motors moving on a two-dimensional continuum ratchet potential, which quantitatively agree with the FLIC experiments. We find that single-headed KIF1A sidestepping can be explained as a consequence of the intrinsic handedness and polarity of the microtubule lattice in combination with the diffusive mechanochemical cycle of the motor.}, URL = {https://www.biorxiv.org/content/early/2019/02/04/536250}, eprint = {https://www.biorxiv.org/content/early/2019/02/04/536250.full.pdf}, journal = {bioRxiv} }