A biophysical model for the formation of mitotic spindle bipolarity

Mitotic spindles use an elegant bipolar architecture to segregate duplicated chromosomes with high fidelity. Bipolar spindles form from a monopolar initial condition; this is the most fundamental construction problem that the spindle must solve. Microtubules, motors, and cross-linkers are important for bipolarity, but the mechanisms necessary and sufficient for spindle assembly remain unknown.

We describe a physical model that exhibits de novo bipolar spindle formation. We begin with physical properties of fission-yeast spindle pole body size and microtubule number, kinesin-5 motors, kinesin-14 motors, and passive cross-linkers. Our model agrees quantitatively with our experiments in fission yeast, thereby establishing a minimal system with which to interrogate collective self-assembly.

By varying the features of our model, we identify a set of functions essential for the generation and stability of spindle bipolarity. When kinesin-5 motors are present, their bidirectionality is essential, but spindles can form in the presence of passive cross-linkers alone. We also identify characteristic failed states of spindle assembly—the persistent monopole, X spindle, separated asters, and short spindle, which are avoided by the creation and maintenance of antiparallel microtubule overlaps. More recently, we have begun to investigate the mechanisms responsible for chromosome bi-orientation, correction of kinetochore-microtubule attachment errors, and lost kinetochore capture.