Nano-particles carried by multiple dynein motors: A Self-Regulating Nano-Machine

Abstract

<jats:p>Native cargos achieve efficient intra-cellular active transport by recruiting multiple motors proteins from the cytoplasm. Here we investigate the motion of spherical nano-particles (NPs), acting as model cargos, grafted with flexible polymers, each ending with a nuclear localization signal (NLS) peptide, thereby allowing recruitment of mammalian cytoplasmic dynein. Bead-motility assays show several unique features. As the number of motors increases, the run-time and run-length increase, the longitudinal velocity mean decreases, whereas its width shows a non-monotonous behavior. Moreover, both single and multi-motor NPs perform angular (i.e., projected transverse) motion. Strikingly, the directions of angular and longitudinal motions are correlated, such that retrograde steps are combined with right-handed motion. We formulate a theoretical model to simulate the multi-dynein transported NP. The model builds on a recently theoretical description of single yeast dynein stepping on the curved microtubule surface, modified to account for mammalian dynein, and generalized to include motor-motor elastic and excluded-volume coupling. The simulation results are majorly in agreement with our experimental results. Moreover, long time trajectories exhibit both left- and right- handed helical motion around the MT symmetry axis, consistent with the measured and simulated angular velocity. The model gives further insight into the mechanism of the NP motion and suggests that the NPs are self-regulating the number of participating motors, optimizing between single motor, for obstacle bypassing, and multi-motor behavior, for persistent directional motion. We suggest that native cargos could use a similar mechanism to achieve efficient transport in the crowded cellular environment.</jats:p>