Cooperative Protofilament Switching Emerges from Inter-Motor Interference in Multiple-Motor Transport

TL;DR

This study reveals that groups of kinesin motors exhibit cooperative protofilament switching through inter-motor interference, enhancing cargo navigation along microtubules by dynamically switching between active and surface-associated modes.

Contribution

It introduces a combined experimental and theoretical framework showing how inter-motor interactions induce a novel surface-associated mode in kinesin, improving cargo transport efficiency.

Findings

Kinesin exhibits increased perpendicular motion when in groups.

Inter-motor interference enables a surface-associated diffusion mode.

Kinesin switches between active and surface-associated modes to navigate obstacles.

Abstract

Within living cells, the transport of cargo is accomplished by groups of molecular motors. Such collective transport could utilize mechanisms which emerge from inter-motor interactions in ways that are yet to be fully understood. Here we combined experimental measurements of two-kinesin transport with a theoretical framework to investigate the functional ramifications of inter-motor interactions on individual motor function and collective cargo transport. In contrast to kinesin's low sidestepping frequency when present as a single motor, with exactly two kinesins per cargo, we observed substantial motion perpendicular to the microtubule. Our model captures a surface-associated mode of kinesin, which is only accessible via inter-motor interference in groups, in which kinesin diffuses along the microtubule surface and rapidly "hops" between protofilaments without dissociating from the microtubule. Critically, each kinesin transitions dynamically between the active stepping mode and this weak surface-associated mode enhancing local exploration of the microtubule surface, possibly enabling cellular cargos to overcome macromolecular crowding and to navigate obstacles along microtubule tracks without sacrificing overall travel distance.