Computational Study of Microtubule Networks in Cell Division, Rebekah Adams, UG '21 (2307105)

The dynamics of the meiotic spindle, the macromolecular machine responsible for the segregation of chromosomes and equal partitioning of genetic information during cellular division, are immensely complex and not fully understood. This study involves building computational models of what we consider the most fundamental components for the formation and stability of the meiotic spindle. All calculations were done using Langevin dynamics and kinetic Monte Carlo methods with Cytosim. We modelled microtubules as flexible, soft filaments that undergo dynamic instability. Microtubules are introduced into the system by nucleators that are spatially regulated in a decaying gradient, mimicking the RanGTP pathway in found in cells. Plus-end directed extensile motors (kinesins) and minus-end directed contractile motors (dynein) then organize these microtubules into the desired steady-state structure. Using these components, we aimed to build a two-dimensional bipolar spindle starting from nothing. This would help us quantitatively rationalize how the spindle self-assembles and the cell cycle transitions from prophase up to metaphase. To this end, we systematically varied (i) the microtubule nucleation profile and (ii) the concentration and relative amounts of the two motor proteins and observed how that affected the resultant microtubule networks. From our simulations, we were able to infer some of the necessary physical rules and conditions that must be met in order to assemble and maintain a functional bipolar spindle. We discuss where our conclusions might be particularly important in the context of recent theoretical and experimental studies of the spindle.