Mechanical positioning of multiple nuclei in muscle cells

Angelika Manhart, Stefanie Windner, Mary Baylies, Alexander Mogilner

Research output: Contribution to journalArticle

Abstract

Many types of large cells have multiple nuclei. In skeletal muscle fibers, the nuclei are distributed along the cell to maximize their internuclear distances. This myonuclear positioning is crucial for cell function. Although microtubules, microtubule associated proteins, and motors have been implicated, mechanisms responsible for myonuclear positioning remain unclear. We used a combination of rough interacting particle and detailed agent-based modeling to examine computationally the hypothesis that a force balance generated by microtubules positions the muscle nuclei. Rather than assuming the nature and identity of the forces, we simulated various types of forces between the pairs of nuclei and between the nuclei and cell boundary to position the myonuclei according to the laws of mechanics. We started with a large number of potential interacting particle models and computationally screened these models for their ability to fit biological data on nuclear positions in hundreds of Drosophila larval muscle cells. This reverse engineering approach resulted in a small number of feasible models, the one with the best fit suggests that the nuclei repel each other and the cell boundary with forces that decrease with distance. The model makes nontrivial predictions about the increased nuclear density near the cell poles, the zigzag patterns of the nuclear positions in wider cells, and about correlations between the cell width and elongated nuclear shapes, all of which we confirm by image analysis of the biological data. We support the predictions of the interacting particle model with simulations of an agent-based mechanical model. Taken together, our data suggest that microtubules growing from nuclear envelopes push on the neighboring nuclei and the cell boundaries, which is sufficient to establish the nearly-uniform nuclear spreading observed in muscle fibers.

Original languageEnglish (US)
Article numbere1006208
JournalPLoS Computational Biology
Volume14
Issue number6
DOIs
StatePublished - Jun 1 2018

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Muscle
myocytes
Muscle Cells
positioning
Positioning
Nucleus
muscle
Cells
Cell
Microtubules
microtubules
cells
Cell Nucleus
Muscles
Microtubule-Associated Proteins
Fibers
Reverse engineering
Skeletal Muscle Fibers
Nuclear Envelope
Systems Analysis

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Modeling and Simulation
  • Ecology
  • Molecular Biology
  • Genetics
  • Cellular and Molecular Neuroscience
  • Computational Theory and Mathematics

Cite this

Mechanical positioning of multiple nuclei in muscle cells. / Manhart, Angelika; Windner, Stefanie; Baylies, Mary; Mogilner, Alexander.

In: PLoS Computational Biology, Vol. 14, No. 6, e1006208, 01.06.2018.

Research output: Contribution to journalArticle

Manhart, Angelika ; Windner, Stefanie ; Baylies, Mary ; Mogilner, Alexander. / Mechanical positioning of multiple nuclei in muscle cells. In: PLoS Computational Biology. 2018 ; Vol. 14, No. 6.
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