Title: Connecting Molecules and Forces with Rings and Loops

Abstract: Animal cell shape is dictated by the actomyosin cytoskeleton, including the membrane-apposed cortex. The molecular parts list of the cortex is well-characterized, and included the dynamic F-actin polymers, myosin family motor proteins, and myriad non-motor crosslinkers that scaffold the cytoskeleton, the membrane, and regulatory proteins. It is less well-understood how the cytoskeleton is arranged and re-arranged to generate the forces that establish and change cell shape. We use the highly dynamic cytokinetic ring and the dynamically stable cortex of a germline syncytium as models for the actomyosin cytoskeleton. We use C. elegans as a fast, small, cheap, optically clear, and accessible model organism for these and other studies. We measure the kinetics of cell shape change and protein enrichment, in control cells and those depleted by RNAi of target proteins. Via collaborations, we use various mathematical modeling approaches in which the actomyosin cytoskeleton is approximated as an active gel. We use measurements to constrain our models, and compare in vivo measurements to model outputs to test our model assumptions. Our multidisciplinary work makes testable predictions about cytoskeletal organization and remodeling, the magnitude of forces, and conserved proteins’ roles.