Mitotic cells contract actomyosin cortex and generate pressure to round against or escape epithelial confinement

Abstract

Little is known about how mitotic cells round against epithelial confinement. Here, we engineer micropillar arrays that subject cells to lateral mechanical confinement similar to that experienced in epithelia. If generating sufficient force to deform the pillars, rounding epithelial (MDCK) cells can create space to divide. However, if mitotic cells cannot create sufficient space, their rounding force, which is generated by actomyosin contraction and hydrostatic pressure, pushes the cell out of confinement. After conducting mitosis in an unperturbed manner, both daughter cells return to the confinement of the pillars. Cells that cannot round against nor escape confinement cannot orient their mitotic spindles and more likely undergo apoptosis. The results highlight how spatially constrained epithelial cells prepare for mitosis: either they are strong enough to round up or they must escape. The ability to escape from confinement and reintegrate after mitosis appears to be a basic property of epithelial cells.

Coupling changes in cell shape to chromosome segregation

“…Simultaneously, the mixing of cytoplasm and nucleoplasm induced by the loss of the nuclear compartment is likely to induce a sudden drop in the concentration of proteins localized to only one of the two compartments -inducing profound changes in cellular biochemistry and cytoarchitecture. This is augmented by osmotic swelling 59 and a sudden influx of water, leading to a significant (>10%) increase in cell volume that is independent of the actin cytoskeleton 60,61 and a dramatic increase in cell height 59,62,63 . In combin ation, changes in cell architecture, actin remodelling, cell-substrate adhesion and osmotic swelling, cause cells to assume a spherical shape by the time they have assembled a metaphase plate (FIGS 1,3a).…”

“…Although spherical mitotic cells resemble nonadherent interphase cells, their mechanical properties are profoundly differ ent 13,59,[63][64][65] . In fact, entry into mitosis is accompanied by a rapid, nearly tenfold decrease in cell compliance (equivalent to an increase in cell stiffness).…”

“…These forces are sufficient to deform neighbouring cells within a crowded epithelial tissue 11,66 (FIG. 3b), can drive the api cal movement of cell mass in a columnar epithelium 63 and are strong enough to induce morphogenetic tissue buckling in the developing fly and lumen growth in zebrafish epithelial tissues 66,67 . Thus, the stable, rounded shape that is character istic of metaphase cells reflects a balance of forces (FIG.…”

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

“…MR occurs in detached cells, cells adherent to a substrate as well as in epithelial cells within tissues [10–12]. MR in epithelia coincides with an increased polymerization of actomyosin at the cell cortex, which results in an increase in cortical stiffness [4,11].…”

Pancreatic cancer: a mechanobiology approach

“…For example, Saez and colleagues developed an elastic pillar array that recapitulated the mechanical environment of epithelial sheets that allowed the study of the mechanical factors influencing mitosis with unprecedented detail [57]. Also, Ghassemi et al extended the applicability of these sensors by fabricating pillars of submicron sizes, which enabled many cellular processes that could not be observed with the micropillars [58].…”