Pushing or pulling? A 2D model of the mitotic spindle.

The mitotic spindle is a microtubule-based subcellular apparatus that is responsible for segregating replicated DNA equally into two daughter cells. The placement of the daughter cells within a tissue is determined by the orientation of the spindle at metaphase, just before the DNA separates. In animal cells, spindle orientation is thought to be governed by forces that act on astral microtubules, which are those microtubules that grow towards the cell boundary (cortex), rather than the DNA. The canonical model for spindle orientation holds that motor protein complexes on the cell cortex exert a pulling force that reels the spindle into alignment. Less attention has been paid to a non-exclusive possibility, which is that spindle orientation relies on a pushing force generated by growing microtubules that hit the cortex. These models have proven difficult to distinguish using experimental manipulation. We are therefore building a minimalistic computational model in 2D to test how these possibilities could affect spindle dynamics and daughter cell positioning. Our preliminary results suggest that pushing forces are required for proper spindle positioning and angle alignment meaning that the canonical model is incomplete. Our ongoing work is to study the mechanism of microtubule-cortex interaction and the effects of cell shape and motor protein complex localization pattern on spindle orientation.