Mechanical positioning of multiple nuclei in muscle cells

摘要

Author summary How the cell organizes its interior is one of the fundamental biological questions, but the principles of organelles’ positioning remains largely unclear. In this study we use computational modeling and image analysis to elucidate mechanisms of positioning of multiple nuclei in muscle cells. We start with the general hypothesis, supported by published data, that a force balance generated by microtubule asters growing from the nuclei envelopes are responsible for pushing or pulling neighboring nuclei and cell boundaries, and that these forces position the nuclei. Instead of assuming what these forces are, we computationally screen all possible forces by comparing predictions of hundreds simple mechanical models to experimentally measured nuclear positions and shapes in hundreds of Drosophila muscle cells. This screening results in the model, according to which microtubules from one nucleus push away both neighboring nuclei and cell boundaries. We also perform detailed stochastic simulations of the only surviving model with individual growing, pushing and bending microtubules. This model predicts subtle features of nuclear patterns, all of which we confirm experimentally. Our study sheds light on general principles of organelle positioning.