Jan 25, 2016

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

BioRxiv : the Preprint Server for Biology
Ali NematbakhshMark S 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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Mentioned in this Paper

Regulation of Biological Process
Cell Division
Neoplasms
Epithelium
Apical Membrane
Structure of Cortex of Kidney
Cell Growth
Apical
Cytoplasmic
Tumor Cells, Malignant

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