Physical determinants of bipolar mitotic spindle assembly and stability in fission yeast

Department of Physics, University of Colorado Boulder

During cell division, mitotic spindles use an elegant bipolar architecture to segregate duplicated chromosomes with high fidelity. Bipolar spindles form from a monopolar initial condition, a fundamental construction problem that the spindle must solve. Specific biological ingredients (microtubules, motors, and crosslinkers) are important for spindle bipolarity, but the mechanisms necessary and sufficient for spindle assembly remain unknown. This talk will develop the necessary background on cell division, spindles, and the molecular players for spindle assembly; no prior biology knowledge is required.

We have developed a stochastic model that exhibits de novo bipolar spindle formation. We began with previously published data on fission-yeast spindle-pole-body size and microtubule number, kinesin-5 motors, kinesin-14 motors, and passive crosslinkers. Our model results agree quantitatively with our experiments in fission yeast, thereby establishing a minimal system with which to interrogate collective self assembly. We identify a set of functions essential for the generation and stability of spindle bipolarity in the model. When kinesin-5 motors are present, their bidirectionality is essential, but spindles can form in the presence of passive crosslinkers alone. We identify characteristic failed states of spindle assembly, which are avoided by creation and maintenance of antiparallel microtubule overlaps.