Theory of Cytoskeletal Reorganization during Cross-Linker-Mediated Mitotic Spindle Assembly

Biophys J. 2019 May 7;116(9):1719-1731. doi: 10.1016/j.bpj.2019.03.013. Epub 2019 Apr 13.

Abstract

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

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Biomechanical Phenomena
  • Microtubules / metabolism
  • Mitosis*
  • Models, Biological*
  • Monte Carlo Method
  • Spindle Apparatus / metabolism*
  • Stochastic Processes