Bidirectional cargo transport by kinesin and dynein is essential for cell viability and defects are linked to neurodegenerative diseases. Computational modeling suggests that the load-dependent off-rate is the strongest determinant of which motor ‘wins’ a kinesin-dynein tug-of-war, and optical tweezer experiments find family-dependent differences in the sensitivity of detachment to load, with kinesin-3 > kinesin-2 > kinesin-1. However, in reconstituted kinesin-dynein pairs vitro, all three
