Multi-scale computational study of the mechanical regulation of cell mitotic rounding in epithelia

PLoS Computational Biology
Ali NematbakhshMark Alber

Abstract

Mitotic rounding during cell division is critical for preventing daughter cells from inheriting an abnormal number of chromosomes, a condition that occurs frequently in cancer cells. Cells must significantly expand their apical area and transition from a polygonal to circular apical shape to achieve robust mitotic rounding in epithelial tissues, which is where most cancers initiate. However, how cells mechanically regulate robust mitotic rounding within packed tissues is unknown. Here, we analyze mitotic rounding using a newly developed multi-scale subcellular element computational model that is calibrated using experimental data. Novel biologically relevant features of the model include separate representations of the sub-cellular components including the apical membrane and cytoplasm of the cell at the tissue scale level as well as detailed description of cell properties during mitotic rounding. Regression analysis of predictive model simulation results reveals the relative contributions of osmotic pressure, cell-cell adhesion and cortical stiffness to mitotic rounding. Mitotic area expansion is largely driven by regulation of cytoplasmic pressure. Surprisingly, mitotic shape roundness within physiological ranges is most sens...Continue Reading

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Citations

Aug 17, 2020·Physical Review. E·Zong-Yuan LiuHuajian Gao
Aug 28, 2020·Frontiers in Cell and Developmental Biology·Anna V TaubenbergerHelen K Matthews
Aug 31, 2021·Biophysical Journal·Vijay Velagala, Jeremiah J Zartman

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