UC Berkeley

Motor proteins take part in the organization and division of eukaryotic cells by using their ability to move unidirectionally along the cytoskeletal tracks. While kinesin and myosin motor families have members that move towards either end of actin and microtubules, respectively, all dynein motors exclusively move towards the minus-end of microtubules. Previous studies reported that dynein asymmetrically responds to external forces, moving faster when pulled forward, while resisting backward movement under hindering forces. I hypothesized that this asymmetry enables dynein to harness energy from external force fluctuations for faster movement towards the minus-end.

In my doctoral work, I have shown that dynein can harness energy from cytoskeletal fluctuations. Using optical trapping techniques, I have characterized how external forces affect the velocity of dynein motility in the presence and absence of ATP. The results demonstrated that dynein forms an asymmetric slip bond with the microtubule. Using an oscillatory optical trapping assay, I showed that dynein can rectify force fluctuations to move towards the microtubule minus-end in the absence of ATP. Dynein was capable of moving towards the minus-end, even when the net force is in the plus-end direction. In the presence of ATP, dynein was able to move faster, generate power from force fluctuations, and stand against higher resistive forces. I developed a mathematical model that connects the force-induced release rate of dynein monomers with the force-velocity relationship of dynein dimers to describe dynein’s reaction to force.