3D Model of Cytokinetic Ring Assembly in Fission Yeast

Abstract

During fission yeast cytokinesis, actin filaments are nucleated in random directions by cortical Cdc12 and captured by myosin-II motors from neighboring nodes, exerting forces that pull them together into a contractile ring. Contractile ring assembly has been previously described using a stochastic 2D computational model based on a “search, capture, pull and release” mechanism (SCPR). In this model, actin filaments are assumed to polymerize along the cell membrane, consistent with enhanced concentration of actin filaments near the cell membrane in experiments. Recent observations in mutant and wild-type cells have suggested that actin filaments nucleated in the cytoplasm and in non-medial locations can also participate into the assembly of the cytokinetic ring as well as in clump, star, and meshwork actomyosin morphologies. The relative contributions of the non-medially nucleated actin filaments has been debated. In order to examine these effects that involve 3D dynamics and to better understand the mechanisms that confine actin filaments along the cell surface, we extended the SCPR model to 3D. In this model semiflexible actin filaments (represented as beads connected by springs) grow from nodes and they can be captured by myosin in neighboring nodes. Cross-linking by alpha-actinin and fimbrin is represented by an attractive interaction between filament beads. We also implemented cytoplasmic formin nucleation and actin cable incorporation into the contractile ring. We quantified the resulting distribution and orientation of actin around the band of myosin nodes and studied the effects of varying model parameter values. We describe the conditions under which ring, clump, transient star and meshwork structures may form along the cell membrane and compare to prior experiments.