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 nano-particles (NPs) grafted with flexible polymers, each ending with a nuclear localization signal peptide, thereby allowing recruitment of mammalian cytoplasmic dynein. Bead-motility assays show several unique motility features, depending on the number of NP-bound motors. NPs perform angular motion, in which the plus-end directed and right-handed motions are correlated. To simulate the system, we formulate a theoretical model that builds on single mammalian dynein properties, generalized to include motor-motor elastic and excluded-volume interactions. We find that long time trajectories exhibit both left- and right-handed helical motion, consistent with the measured angular velocity. The number of participating motors is self-regulated, thus allowing the NP to benefit from alternations between single and multiple transporting motors. Native cargos could use a similar approach to achieve both obstacle bypassing and persistent motion in the crowded cellular environment. Significance Statement The mechanism of active transport of native cargos, such as some viruses, is a long-standing conundrum. Their need for persistence motion towards the nucleus, while bypassing obstacles in the super-crowded intracellular milieu, requires sophisticated natural design. To fathom this machinery, we study a smartly designed nano-particle that recruits several dynein motor-proteins from the cytoplasm. Motility assays and model simulations reveal long run-times, long run-lengths, and helical motion around the microtubule symmetry axis. Moreover, the nano-particles self-regulate the number of dyneins participating in the motion, which optimizes its motility properties. We suggest that alternating between single motor motility, which we believe is beneficial for obstacle bypassing, and multiple motor states, which engender persistent motion towards the nucleus, the NP achieves optimal transport efficiency.