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Within living cells, the transport of cargo is accomplished by groups ofmolecular motors. Such collective transport could utilize mechanisms whichemerge from inter-motor interactions in ways that are yet to be fullyunderstood. Here we combined experimental measurements of two-kinesin transportwith a theoretical framework to investigate the functional ramifications ofinter-motor interactions on individual motor function and collective cargotransport. In contrast to kinesin's low sidestepping frequency when present asa single motor, with exactly two kinesins per cargo, we observed substantialmotion perpendicular to the microtubule. Our model captures asurface-associated mode of kinesin, which is only accessible via inter-motorinterference in groups, in which kinesin diffuses along the microtubule surfaceand rapidly "hops" between protofilaments without dissociating from themicrotubule. Critically, each kinesin transitions dynamically between theactive stepping mode and this weak surface-associated mode enhancing localexploration of the microtubule surface, possibly enabling cellular cargos toovercome macromolecular crowding and to navigate obstacles along microtubuletracks without sacrificing overall travel distance.

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