A first-principles geometric model for dynamics of motor-driven centrosomal asters

Abstract

The centrosomal aster is a mobile cellular organelle that exerts and transmits forces necessary for nuclear migration and spindle positioning. Recent experimental and theoretical studies of nematode and human cells demonstrate that pulling forces on asters by cortical force generators are dominant during such processes. We present a comprehensive investigation of a first-principles model of aster dynamics, the S-model (S for stoichiometry), based solely on such forces. The model evolves the astral centrosome position, a probability field of cell-surface motor occupancy by centrosomal microtubules (under an assumption of stoichiometric binding), and free boundaries of unattached, growing microtubules. We show how cell shape affects the centering stability of the aster, and its transition to oscillations with increasing motor number. Seeking to understand observations in single-cell nematode embryos, we use accurate simulations to examine the nonlinear structures of the bifurcations, and demonstrate the importance of binding domain overlap to interpreting genetic perturbation experiments. We find a rich dynamical landscape, dependent upon cell shape, such as internal equatorial orbits of asters that can be seen as traveling wave solutions. Finally, we study the interactions of multiple asters and demonstrate an effective mutual repulsion due to their competition for cortical force generators. We find, amazingly, that asters can relax onto the vertices of platonic and non-platonic solids, closely mirroring the results of the classical Thomson problem for energy-minimizing configurations of electrons constrained to a sphere and interacting via repulsive Coulomb potentials. Our findings both explain experimental observations, providing insights into the mechanisms governing spindle positioning and cell division dynamics, and show the possibility of new nonlinear phenomena in cell biology.