Sensitivity of Multiple-Kinesin Transport to Microtubule Lattice Defects

Abstract

Microtubules are fundamental biopolymers in cells, formed via self-assembly of tubulin dimers. Defects in microtubule lattices have been observed, including point defects (missing tubulin dimers) and line defects (protofilament disruption). Microtubule-based molecular motors enable long-range transport in cells. Potential impact of microtubule lattice defects on intracellular transport is not yet understood. Here we vary microtubule polymerization conditions to uncontrollably tune defect presence in microtubule lattices, and use single-molecule-type optical trapping experiments to investigate the impact of such defect on multiple-kinesin transport. We find that kinesin-based cargoes pause preferentially at specific locations along individual microtubules, and that the pause frequency and duration increase with increasing presence of defects in microtubules. Additionally, we find that the dissociation rates of multiple-kinesin-based cargoes are also strongly dependent on the specific microtubules they travel along. Taken together, our study highlights a previously unexplored, and important role of microtubule lattice assembly in controlling intracellular transport.