Hydrostatic pressure and the actomyosin cortex drive mitotic cell rounding

Abstract

During mitosis, adherent animal cells undergo a drastic shape change, from essentially flat to round. Mitotic cell rounding is thought to facilitate organization within the mitotic cell and be necessary for the geometric requirements of division. However, the forces that drive this shape change remain poorly understood in the presence of external impediments, such as a tissue environment. Here we use cantilevers to track cell rounding force and volume. We show that cells have an outward rounding force, which increases as cells enter mitosis. We find that this mitotic rounding force depends both on the actomyosin cytoskeleton and the cells' ability to regulate osmolarity. The rounding force itself is generated by an osmotic pressure. However, the actomyosin cortex is required to maintain this rounding force against external impediments. Instantaneous disruption of the actomyosin cortex leads to volume increase, and stimulation of actomyosin contraction leads to volume decrease. These results show that in cells, osmotic pressure is balanced by inwardly directed actomyosin cortex contraction. Thus, by locally modulating actomyosin-cortex-dependent surface tension and globally regulating osmotic pressure, cells can control their volume, shape and mechanical properties.

Mitotic cell rounding and epithelial thinning regulate lumen growth and shape

“…Here we used laser microsurgery to analyse the mechanics of mitotic rounding cells in the context of a vertebrate epithelium. In concordance with the demonstration that a rounded cell can exert forces against other structures in vitro 36 , we observed a related behaviour in vivo, with changes in shape occurring during rounding, exerting pulling forces on the tissue. This constitutes a direct mechanical action of a single-cell deforming an epithelium.…”

“…Similar to the actomyosin requirement to round when a cultured cell adheres to the substrate 36 , we propose that the actomyosin cortex in the rounding cell pulls the epithelial walls as a consequence of its connections with the surrounding cells. Moreover, the bleb formed after laser severing also highlights the importance of both intracellular hydrostatic pressure and the actomyosin cortex during rounding in vivo in an epithelial context, whose interplay was previously shown to be required for rounding in vitro 36 . On top of these intrinsic otic forces, surrounding tissues could also provide mechanical constraints and impinge on the otic vesicle and lumen shape, a question that still needs to be addressed.…”

“…The mechanics of mitotic cell rounding has been analysed in cultured cells 36 . Laser ablation was used to analyse in vivo the forces generated by actomyosin structures organized in apical layers or cables 29,37,38 .…”

The metastatic cancer cell cortex: An adaptation to enhance robust cell division in novel environments?

“…These shape changes, both in cell culture and in vivo [15], depend on the actin cytoskeleton, which is re-organized upon mitotic entry to form a cortical mesh that underlies the plasma membrane [17]. As well as driving cell shape change, the re-organization of cortical actin in mitosis also counters osmotic swelling forces [18] and provides mitotic cells with their characteristic mechanical rigidity [16,19].…”

Rapid dynamics of cell-shape recovery in response to local deformations

“…contributions from osmotic and hydrostatic pressure, as has been shown during bleb formation 45 and mitosis 46 .…”