Dynamic Actomyosin Network Morphology in 3D Model of Cytokinetic Ring Assembly

Abstract

At the onset of cytokinesis in fission yeast (a model organism for studying mitosis), the locations of actin filament nucleation by formins shift from the cell tips to the cell middle. These actin filaments are captured by myosin motors bound to medial cortical nodes and bundled by crosslinking proteins, in order to form a ring. The myosin motors exert forces on the actin filaments, resulting in net pulling of nodes and filaments towards the cell equator, while cross-linking interactions help align actin filaments into a single bundle. We used these mechanisms in a 3D computational model of ring assembly, with semiflexible actin filaments growing from formins at the cell tips and at the medial cell cortex, capturing and pulling of filaments by nodes, and cross-linking among filaments through attractive interactions. The model was used to predict profiles of actin density at the cortex, morphologies of condensing node-filament networks, including the transition from actin cables to ring in different conditions of myosin activity and strength of crosslinking. Results show that cross-linking interactions can lead to confinement of actin filaments that grow from medial locations of the cell cortex. We show that the ring formation region in parameter space lies close to regions leading to clumps, meshworks or double rings, and stars/cables. Since boundaries between regions are not sharp, transient structures that resemble clumps, stars and meshworks can appear in the process of ring assembly. The presence of transient nonmedial cables linking the medial region to the cell tips can further modify these boundaries. These results are consistent with prior experiments with mutations in actin filament turnover regulators, myosin motor activity and changes in the concentration of cross linkers that alter the morphology of the condensing network.