Math Biology Seminar: Dr. Angelika Manhart

Many types of large cells have multiple nuclei. In long muscle cells, nuclei are distributed almost uniformly along their length, which is crucial for cell function. However, the underlying positioning mechanisms remain unclear. We examine computationally the hypothesis that a force balance generated by microtubules positions the nuclei. Rather than assuming what the forces are, we allow for various types of forces between pairs of nuclei and between the nuclei and the cell boundary. Mathematically, this means that we start with a great number of potential models. We then use a reverse engineering approach by screening the models and requiring their predictions to fit imaging data on nuclei positions from hundreds of muscle cells of Drosophila larva. Computational screens result in a small number of feasible models, the most adequate of which suggests that the nuclei repel each other and the cell boundary with forces that decrease with distance.

This suggests that microtubules growing from nuclear envelopes push on neighboring nuclei and the cell boundary. We support this hypothesis with stochastic microscopic simulations. Using statistical and analytical tools such as correlation and bifurcation analysis, we make several nontrivial predictions: An increased nuclear density near the cell poles, zigzag patterns in wider cells, and correlations between the cell width and elongated nuclear shapes, all of which we confirm by image analysis of the experimental data.

This is joint work with Mary Baylies, Alex Mogilner and Stefanie Windner.