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Biophys J ; 116(9): 1719-1731, 2019 05 07.
Article in English | MEDLINE | ID: mdl-31010665

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.


Subject(s)
Mitosis , Models, Biological , Spindle Apparatus/metabolism , Biomechanical Phenomena , Microtubules/metabolism , Monte Carlo Method , Stochastic Processes
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