Special Seminar: 3D Stochastic Simulations of Cargo Transport Reveal the Influence of Cargo and Environment

 

Active transport of subcellular cargos along microtubules is essential for organization and function of eukaryotic cells. While we understand much about how single motors are able to generate force to accomplish this transport, little is understood about how properties of the cargo itself and properties of its environment can influence how cargos are transported. To investigate how these properties may influence transport in the cell, we developed a 3D Brownian dynamics simulator of cargo transport which includes cargo shape and motor location on the cargo. We present results describing how cargos navigate microtubule intersections in vitro. These results suggest that tuning intersection geometry may allow the cell to sort cargos based on several properties. We also present simulations which investigate the effects of surface-fluid properties of vesicular cargo and lipid droplets, which have previously been challenging to simulate. Simulations in which motors are free to diffuse in the cargo membrane suggest the possibility that this freedom may allow cargos to both bind rapidly to the microtubule and make efficient use of several motors, a combination which is difficult to achieve when motors are anchored rigidly. The end goal of the simulator is to reveal how changes in cargo or environment properties can drive cargos toward distinct transport outcomes, opening the way for environment-based cargo sorting and, ultimately, navigation and cell-scale spatial organization.