Mechanics of bidirectional cargo transport

Bidirectional cargo transport along microtubules is carried out by the competing activities of dynein and kinesin motors attached to the same cargo. Despite extensive study, the mechanisms that determine the net rate and directionality of transport for specific cargo under specific intracellular conditions remain under debate. A number of studies are consistent with the "tug-of-war" model, which posits that the emergent behavior results from competing activities of oppositely-directed motors. However, published findings from a number of model systems runs counter to predictions from the tug-of-war model. To frame current and future work, this chapter presents a conceptual model of microtubule-based bidirectional transport that highlights six quantitative parameters: motor number, velocity, stall force, run length, detachment force, and reattachment rate. The relative importance of each parameter to the emergent bidirectional transport behavior is discussed, and the state of knowledge for different kinesin and dynein isoforms is discussed. Finally, mechanisms that regulate bidirectional transport are explored, focusing on the underexplored role of membrane fluidity in multi-motor bidirectional transport.