Motor tug-of-war is productive

Atug-of-war between microtubule motors creates cooperation that makes cargo transport a snap, according to a mathematical model from Melanie Müller (Max Planck Institute of Colloids and Interfaces, Potsdam, Germany) and colleagues.

Microtubule-based transport runs in two directions: motors such as kinesin pull cargo toward filament plus ends, whereas dynein heads to minus ends. Both motor types can bind at once to a single cargo, suggesting that they should hinder each other's progress.

Some researchers propose that the two motor sets are coordinated by a regulatory complex to ensure that only one team is bound to the track at a given time. But the new model indicates that motors can fight it out themselves and still bring cargo to its destination.

The motors were characterized mathematically using previously measured properties such as motor speed, strength, and binding and unbinding rates. The calculations revealed that fast, directional transport was possible due to what the authors call an unbinding cascade. Random fluctuations in the number of motors bound to the microtubule give one motor team an advantage. If the force generated by the winning team is enough to detach a losing motor, each remaining losing motor bears a greater force and thus becomes even more likely to fall off until only the winning team is attached.

Small variations in the properties of one motor, such as might be caused by mutations or cellular regulatory pathways, altered the probability that one team or the other would win. Plugging such alterations into the model reproduced actual changes in transport behavior seen in developing fly embryos.

Müller would like to see the model tested further. “I'm not an experimentalist,” she says. “So I hope someone else builds an in vitro assay—bind microtubules to a surface and add beads with both motors attached. If you lower ATP concentrations to decrease motor velocity, does it then do what our model predicts?” The biggest obstacle might be getting dynein, which Müller calls the “diva” of motors, to behave reproducibly in vitro.

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