Mathematical Modeling and Simulations of Centriole Positioning During Mitosis of Cells in Confined Environments

Abstract

In order to properly undergo mitosis, epithelial cells pass through various biological checkpoints that cause cells to round up, stiffen and divide into two daughter cells. These checkpoints are influenced by biochemical and mechanical factors. Contrary to normal cell division, confined oncogenic cells are able to forgo mitotic rounding and proceed to divide into three to five viable progeny. Why cancerous cells are able to undergo mitosis in confined compact environments is not well understood. We hypothesize that success with confined cell division is at least partly driven by changes in the mechanistic properties and cortical rigidity of cancer cells. To test this hypothesis, we simulate microtubule-motor assembly driven mitotic spindle formation and the alignment of chromosomes along the metaphase plate as the cell rounds up during mitosis. We simulate the cell rounding process with and without confinement and identify the differences in spindle formation dynamics and spindle structure in the two scenarios. These findings will provide insights into the mechanistic pathways driving cancer cell proliferation during tumor growth.