Biophysics of centrosome separation and centrosome-nucleus association

The centrosome is the primary microtubule-organizing center in animal cells. At the start of cell division, the two centrosomes migrate towards the opposite poles of the nucleus. Their positioning is crucial for proper bipolar spindle assembly and for accurate chromosome segregation and cell division. Previous studies have identified many proteins involved in centrosome separation and centrosome-nucleus association; however, the cellular and biophysical mechanisms driving these processes remain ill-understood. Three alternative models have been proposed: pushing forces between antiparallel overlapping microtubules from the two centrosomes, pulling forces from cortically-bound force generators, and pulling forces from nuclear-bound force generators. Here, we combine quantitative microscopy and mathematical modeling and simulation to determine which of these models (if not all) account for centrosome positioning in early C. elegans embryo. We will present experiments where we used laser ablation to sever different microtubules populations and directly test these models. We will also present large-scale simulations of microtubules and their interactions with force-generators on the cell cortex and the nucleus.