Intracellular cargo transport is determined by motors, cargo, and environment
Abstract
Eukaryotic cells are divided into a complex system of compartments, with their spatial organization ever-changing to enable cell functions. For example, in neurons, packages of neurotransmitters are transported from the cell body, down axons, to synapses, where their delivery mediates learning and memory. Phagosomes are transported to meet lysosomes, which fuse to kill pathogens. We know a great deal about the kinesin, dynein, and myosin molecular motors which do mechanical work to drive this motion, as well as the microtubule and actin tracks they are transported along. However, how the many different cargos in a cell are transported using largely the same sets of motors and tracks, but to different outcomes, remains largely a mystery. To understand how cargos can be directed, we build a model of cargo movement at the scale of a cargo. We build a simple model of how motors work from the details known in vitro, then incorporate the physics of a small solid body in a fluid. We apply this model to give insight into several problems. We show that when two microtubules cross at an intersection, they interact with motor and cargo dynamics to dictate outcomes that depend on geometry of the intersection.In another study, we show that organization of motors on the cargo surface can drive different transport outcomes. When motors are attached rigidly to the surface of a cargo, the cargo faces a tradeoff between fast binding and efficient transport. However, when motors are free to diffuse in the cargo membrane, both are possible. In a third study, we take and analyze data on how cargos bind in vitro, and show that a mismatch between model prediction and experimental outcomes provides insight into the behavior of motor molecules. Overall, these studies show that looking at intracellular cargos as 3D objects can provide insight into how cargo transport functions in the cell, as well as providing a bedrock for understanding how and why cells may manipulate the behaviors that emerge from the individual components when they are put together.