Driving Forces for Microtubule Transport in the Mitotic Spindle*

The mitotic spindle is an active polymeric suspension made up of polar microtubules, chemically-reactive proteins, and molecular motors self-assembled for the purpose of capturing and segregating chromosomes during cell division. This self-assembly is orchestrated by a signaling gradient of the small protein RanGTP that emanates from the chromosomes. We present a mesoscale continuum theory that coarsely describes the concentration field of microtubules in a RanGTP gradient, accounting for the dynamic polymerization of tubulin as well as the RanGTP-mediated autocatalytic branching nucleation of microtubules. The analytic results are compared to numerical simulations of the stochastic chemical kinetics as well as experiments conducted in Xenopus laevis meiotic extracts. These data motivate the hypothesis that microtubules are stabilized in the presence of RanGTP, biasing their transport up the RanGTP gradient towards chromosomes. This stabilization manifests itself as a phoretic drift velocity of the microtubules relative to the suspending fluid, which we explore analytically as well as present preliminary experimental findings.