Collective intracellular cargo transport by multiple kinesins on multiple microtubules

Abstract

The transport of intracellular organelles is accomplished by groups of molecular motors, such as kinesin, myosin, and dynein. Previous studies have demonstrated that the cooperation between kinesins on a track is beneficial for long transport. However, within crowded three-dimensional (3D) cytoskeletal networks, surplus motors could impair transport and lead to traffic jams of cargos. Comprehensive understanding of the effects of the interactions among molecular motors, cargo, and tracks on the 3D cargo transport dynamics is still lack. In this work, a 3D stochastic multiphysics model is introduced to study the synergistic and antagonistic motions of kinesin motors walking on multiple mircotubules (MTs). Based on the model, we show that kinesins attaching to a common cargo can interact mechanically through the transient forces in their cargo linkers. Under different environmental conditions, such as different MT topologies and kinesin concentrations, the transient forces in the kinesins, the stepping frequency and the binding and unbinding probabilities of kinesins are changed substantially. Therefore, the macroscopic transport properties, specifically the stall force of the cargo, the transport direction at track intersections, and the mean-square displacement (MSD) of the cargo along the MT bundles vary over the environmental conditions. In general, conditions that improve the synergistic motion of kinesins increase the stall force of the cargo and the capability of maintaining the transport. In contrast, the antagonistic motion of kinesins temporarily traps the cargo and slows down the transport. Furthermore, this study predicts an optimal number of kinesins for the cargo transport at MT intersections and along MT bundles.