Molecular Motor Organization and Mobility on Cargos Can Overcome a Tradeoff between Fast Binding and Run Length

Eukaryotic cells transport cargos, including organelles like lipid droplets and mitochondria, along microtubule tracks using molecular motors. Different cargo are in some cases routed to different subcellular locations, which is essential for organization of the cell interior in space and time. While a great deal is known about the single molecule properties of motors, it is still unclear how the cell coordinates these motors to achieve cargo-specific transport outcomes. One possible mode of regulation is through the organization and mobility of motors on the surface of the cargo. In this work we use physics-based 3D mathematical modeling to investigate how cargos are transported under different assumptions of motor anchoring. We compare cases where motors are free to diffuse in the cargo membrane to cases where motors are rigidly anchored to the cargo with different distributions. We find that different modes of anchoring give rise to differences in transport properties, such as cargo binding rate to the microtubule, run lengths, and forces generated. Cargos with clustered motors are transported efficiently, but are slow to bind to a nearby microtubule. Cargos with motors dispersed rigidly on their surface bind the microtubule quickly, but are not transported efficiently. Cargos with freely-diffusing motors bind the microtubule quickly, and are transported more efficiently than the rigid-dispersed arrangement, although not as efficiently as the clustered arrangement. These results point to a functional role for recently observed changes in motor organization on cargos in the cell. They also suggest motor diffusivity as a control point the cell may use to differentially transport types of cargos, either by using adaptor proteins with different membrane anchors or by controlling lipid composition of the cargo membranes.