A Cell's Life Under Confinement: Growth, Division and Migration When Space is Limited

Abstract

In tissues, cells have their physical space constrained by neighboring cells and extracellular matrix. In the recent years, we have developed simple and versatile devices to precisely and dynamically control this confinement parameter in cultured cells. I will present results we obtained on the effect of forces and confinement on dividing and migrating cells. Early in mitosis, cells round up by pushing on their surroundings. This is essential to ensure enough space to assemble a proper mitotic spindle. In prometaphase and metaphase, cell shape, as well as forces acting on the cell, together affect the orientation of the mitotic spindle, setting the division axis. Later in the division process, daughter cells re-adhere and spread, while the cytokinetic process is not yet finalized. During this late step, forces cells exert on each other and on the substrate regulate the final abscission process. Confinement also strongly affects the mode of migration, eliciting fast amoeboid migration of weakly adherent cells. Finally I will present a new method to accurately follow volume of single cells on long timescales. We found, for all cell types we measured, that cell volume homeostasis is mostly based on the fact that smaller cells have a longer cell division cycle, a process well established for yeast cells, but which was thought to be absent in animal cells. We also found that when cells enter mitosis, they very significantly increase their volume, due to osmotic swelling, a feature that, together with cortical stiffening, might help them to push on their neighbors and round up when dividing under confinement in a tissue.