Mechanisms of Cooperation in Systems of Multiple Processive Motors
Diehl, Michael R.
Doctor of Philosophy
The inside of a eukaryotic cell is a highly organized microscale factory that shuttles components that are created or obtained in one place for use or further modification in another. Diffusion cannot accomplish the feat of translocating an object in the cytoplasm to a particular location that is a micron or more away in a timely fashion, so cells rely instead on processive motor proteins. Microtubule motor proteins are enzymes that harness the chemical energy from ATP hydrolysis to produce force and carry vesicles, membrane-bound organelles, and other cargos along paths in the cell's microtubule filament network to their destinations in the cytoplasm. These proteins recognize the polarity of the microtubule, and different classes of motors walk in different directions with respect to this polarity, giving the cell control over the direction in which a cargo is carried. It has been observed experimentally that many cargos are carried by more than one motor simultaneously, and that these multiple-motor systems can consist both of motors of the same type and of varying numbers of motors of different types. Multiple-motor systems present the possibilities of both enhanced transport performance and of tunable behavior, where the number, type, and arrangement of motors on a group of cargos can be modulated by the cell like an analog-style control to induce those cargos to arrive at a particular distribution of locations in the cytoplasm. In order to resolve the mechanisms by which these things might occur, the combination of experimental and theoretical studies in this thesis focus on the relationship between the basic biophysical properties of the constituent motors in small multiple-motor systems and the degree and nature of the cooperation observed, from the standpoint of several relevant metrics. The results highlight the importance of both the mechanochemistry of the motors and the geometry of the system itself, and offer substantial new insights into why different classes of motors cooperate to different extents, with broad implications.
Biological sciences; Molecular motors; Dynein; Kinesin; Biophysics