UC Merced

Molecular motors such as kinesin-1 drive the active and long-range transport of materials inside of our cells. This transport process is highly regulated, as these cellular cargos need to reach their destinations in a timely manner to maintain the proper function of the cell. Indeed, dysfunctions in this process have been linked to neurodegenerative diseases such as Lou Gehrig’s disease. Kinesins single motor properties play a central role in this regulatory process, as these regulatory factors often act by altering these properties. A major focus of my research was how kinesin-1 detachment rate increases with force and how it is sensitive to the direction of the force. In my thesis study I employed Monte Carlo simulations to investigate the role of kinesins force-detachment kinetics in tuning key transport metrics such as the distance the cargo travels and the velocity of the cargo. I found that kinesins asymmetric force response results in a shorting effect on the cargos run length, as a result of the cargo random thermal motion (chapter 3). This diffusion-based shortening is countered by viscous drag, leading to an unexpected, non-monotonic variation in run length as viscous drag increases. Next, I found that the cargos run length is sensitive to slight changes in the average number of motors on the cargo and how this sensitivity can be tuned by kinesins detachment and attachment rates (chapter 4). Next, I explore how alterations to kinesins force-detachment kinetics, which can arise from macromolecular crowding, can impact the average velocity of cargos carried by more than one motor (chapter 5). Finally, a major part of my PhD experience has been mentoring undergraduates in simulation-based research, for many students this is their first-time doing research. Thus, I have created a guide of useful resources to engage future undergraduate students in similar simulation-based research projects (chapter 7).