Microtubule dynamics modulate cargo run length in intracellular transport

Long-distance cargo transport within cells is critical for maintaining cellular organization and function. While extensive in vitro reconstitution and live cell imaging studies have characterized kinesin-based transport, the effects of microtubule dynamics on cargo transport remain poorly understood. In this study, we systematically vary microtubule dynamics to investigate how teams of kinesins transport small cargoes across different network conditions. We recreate four distinct microtubule environments that span the spectrum of cellular dynamics: fully stable networks with Taxol stabilized microtubules, networks with microtubules exhibiting dynamic instability, actively growing networks, and actively shrinking networks induced by katanin. Our systematic approach reveals that microtubule dynamics profoundly influence cargo transport metrics. We observe strong correlations between cargo run length and both microtubule filament length and lattice stability across all conditions. The tubulin nucleotide state (GTP-like versus GDP-like lattices) significantly affects cargo dissociation rates, with more stable GTP-like configurations supporting longer runs. As networks transition from dynamic to growing to stable states, transport characteristics evolve correspondingly, demonstrating that cells could potentially regulate cargo delivery by modulating microtubule dynamics. Most surprisingly, we find that shrinking microtubules in the presence of katanin exhibit unexpectedly low dissociation rates and frequent pausing events, despite active track disruption. This suggests complex stabilizing interactions between motors, cargo, and depolymerizing microtubules.