Deconvolution of the Cellular Force-Generating Subsystems that Govern Cytokinesis Furrow Ingression

Cytokinesis occurs through the coordinated action of several biochemically-mediated stresses acting on the cytoskeleton. Here, we develop a computational model of cellular mechanics, and using a large number of experimentally measured biophysical parameters, we simulate cell division under a number of different scenarios. We demonstrate that traction-mediated protrusive forces or contractile forces due to myosin II are sufficient to initiate furrow ingression. Furthermore, we show that passive forces due to the cell's cortical tension and surface curvature allow the furrow to complete ingression. We compare quantitatively the furrow thinning trajectories obtained from simulation with those observed experimentally in both wild-type and myosin II null Dictyostelium cells. Our simulations highlight the relative contributions of different biomechanical subsystems to cell shape progression during cell division. Author Summary: Cytokinesis, the physical separation of a mother cell into two daughter cells, requires force to deform the cell. Though there is ample evidence in many systems that myosin II provides some of this force, it is also well known that some cell types can divide in the absence of myosin II. To elucidate the mechanisms by which cells control furrow ingression, we developed a computational model of cellular dynamics during cytokinesis in the social amoeba, Dictyostelium discoideum. We took advantage of a large number of experimentally measured parameters and well-characterized furrow ingression dynamics for a number of different strains. Our simulations demonstrate that there are distinct phases of cytokinesis. Myosin II plays a role providing the stress that initiates furrow ingression. In its absence, however, this force can be supplied by a combination of adhesion and protrusion-mediated stresses. Thereafter, Laplace-like pressures take over and provide stresses that enable the cell to divide. Overall, we show how various mechanical parameters quantitatively impact furrow ingression kinetics, accounting for the cytokinesis dynamics of wild type and mutant cell-lines.