Theory of cytoskeletal reorganization during crosslinker-mediated mitotic spindle assembly

Adam R. Lamson, Christopher Edelmaier, Matthew A. Glaser, and Meredith D. Betterton (2019). Biophysical Journal116, 1719. bioRxiv DOI: 10.1101/419135. DOI: 10.1016/j.bpj.2019.03.013.  Download. 

Cells grow, move, and respond to outside stimuli by large-scale cytoskeletal reorganization. A prototypical example of cytoskeletal remodeling is mitotic spindle assembly, where microtubules nucleate, undergo dynamic instability, bundle, and organize into a bipolar spindle. Key mechanisms of this process include regulated filament polymerization, crosslinking, and motor-protein activity.  Remarkably, fission yeast can assemble a bipolar spindle using only passive crosslinkers. We develop a torque-balance model that describes this reorganization due to dynamic microtubule bundles, spindle-pole bodies, the nuclear envelope, and crosslinkers to predict spindle-assembly dynamics. We compare these results to those obtained with kinetic Monte Carlo-Brownian dynamics simulations, which introduce crosslinker-binding kinetics and other stochastic effects. Our results show that rapid crosslinker reorganization to MT overlaps facilitates crosslinker-driven spindle assembly, a testable prediction for future experiments. Combining these two modeling techniques, we illustrate a general method for studying cytoskeletal network reorganization.