Biomathematics / Computational Biology Colloquium

Mechanical positioning of multiple myonuclei in muscle cells

Speaker: Angelika Manhart, Courant Institute of Mathematical Sciences, New York University

Location: Warren Weaver Hall 1314

Date: Tuesday, March 6, 2018, 12:30 p.m.

Synopsis:

Joint work with Mary Baylies, Alex Mogilner and Stefanie Windner

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. 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 nuclei and the cell boundary. 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.