Department of Chemical Engineering
April 7, 2015
Cytokinesis is the final stage of cell division in which the cell is physically constricted into two.
A central event during cytokinesis is constriction of a tension-producing actomyosin contractile ring. Establishing the role of the contractile ring and the mechanism of tension production has been challenging, because ring constriction is coupled to other processes and ring tension has rarely been measured. Combining theory and experiment, we have studied the fission yeast cytokinetic contractile ring, a uniquely well characterized system for which molecularly explicit mathematical models can be constructed. In fission yeast ring constriction is tightly coupled to septation, the growth of new cell wall in the wake of the constricting ring. Septation entails closure of a septum that encloses the daughter cells in fresh cell wall.
It is commonly thought that the contractile ring drives constriction and sets the constriction rate. We argue that in fission yeast this is not so. First, we find that the yeast ring operates close to the limit of isometric tension, i.e. it regulates its tension but not its rate of shortening. Thus, the constriction rate is not an intrinsic property of the ring. Second, we find that the rate of constriction is set by the septum synthesis apparatus, and the mean septum closure rate is almost unaffected by ring tension. Hypothesizing that septum synthesis is mechanosensitive and mechanically coupled to the ring, a mathematical model shows that ring tension then regulates the circular shape of the septum and thereby ensures proper septum closure. Measurements of roughness statistics of septum edges in live cells are in quantitative agreement with the model.
What is the mechanism of tension production in the ring? Using fission yeast protoplasts we developed a novel method to measure ring tension experimentally. We developed molecularly explicit simulations of the contractile ring that articulate a mechanism of tension production in which incoming components continuously self-organize into a tight actomyosin bundle that generates tensions close to experimental values. A key component of the tension producing mechanism is component anchoring. We show that when part of the ring loses its anchoring, the ring constricts in an entirely distinct ‘fast’ load-free mode, in which the constriction rate is an intrinsic property of the ring related to the load-free myosin velocity. This is the opposite limit to the isometric tension limit that characterizes normal rings. Our predictions are in close agreement with recent experiments by the Mabuchi and Balasubramanian labs.