Nano-particles carried by multiple dynein motors: A self-regulating nano-machine

Native cargos demonstrate efficient intra-cellular active transport. Here we investigate the motion of spherical nanoparticles (NPs) grafted with flexible polymers, each ending with a nuclear localization signal peptide, thereby allowing recruitment of mammalian cytoplasmic dynein. Bead-motility assays, incorporating surface adsorbed microtubules (MTs), show several unique motility features, depending on the number of NP-ligated motors. To elucidate how motor-motor coupling influences these behaviors, we simulate a theoretical model that builds on single mammalian dynein properties, generalized to include motor-motor elastic and excluded-volume interactions. We find, both experimentally and by model simulations, that long-time trajectories exhibit both left-handed and right-handed helical motion, in which the plus-end directed and right-handed motions are correlated. Run-times and run-lengths are enhanced and mean velocities are somewhat suppressed when the number of NP-ligated motors is increased. The number of motors that bind to the MT and participate in the transport is stochastic along trajectories. It is distributed mainly between one to three motors, with the mean growing as the number of NP-ligated motors increases, but not surpassing two. We propose that this self-regulation and stochastic alternations between one, two, and three transporting motors allow our synthetic NP to achieve both persistent motion and obstacle bypassing, which is beneficial for native cargos in the crowded cellular environment.