Moving in the cell : emergent behavior of molecular motor teams in crowded environments

Molecular motors' shuttling of cargo along cytoskeletal filaments is essential for many cellular processes. Motors are mechanoenzymes, and their response to external forces can influence their function. These responses have been largely mapped in dilute in vitro media. The cytosol, however, is crowded with a high concentration of macromolecules which can alter protein conformation, binding rates, reaction kinetics, and, therefore, motor function. Using live cell imaging and single-molecule optical trap measurements, the consequences of macromolecular crowding on cargo transport by kinesin-1 motors is investigated. Surprisingly, it is found that crowding significantly slows transport by teams of motors, while having no effect on single motor velocity. This emergent property of kinesin teams results from the individuals' increased sensitivity to hindering load in a crowded medium. To better understand how individual motor properties lead to emergent properties of kinesin teams, transport by multiple motor teams and their responses to force was simulated in silico. These simulations give results that are similar to those found in the in vitro experiments. Together, these results explain the long observed variability of cargo velocity in living cells, and suggest the use of crowding as a control parameter to study kinesin's mechanochemical cycle