Funds from this grant support a project by Michael Murrell and Enrique De La Cruz, Professors of Biomedical Engineering & Physics, and Biophysics & Biochemistry respectively at Yale, to explore the role that thermodynamics plays in driving cell division. Murrell and De La Cruz hypothesize that the behavior of a cell’s actomyosin cytoskeleton, a ring-shaped network of filaments, motor proteins and connectors that contract to pinch a cell in two, is shaped by thermodynamic principles, and that contraction of the network can be explained by reference to the fact that contracting and dividing would move the skeletal network into a more energetically favorable state. Murrell and De La Cruz will leverage a ‘reconstituted’ actomyosin cytoskeletal network comprised of purified and synthesized cell components which will allow them to study the system’s properties and behaviors outside the complicating environment of a cell. The team will develop new measurement techniques to measure and quantify key thermodynamic parameters of this system: how much entropy is produced, the energy input to the system, the energy output as mechanical work, and the energy lost as heat and validate these measurements to ensure they yield consistent findings (i.e. no missing energy). The team will then apply these techniques to various configurations of the system, measuring how efficiency varies with system structure, composition, and dynamics. They will then insert the artificial network into a cell-sized lipid membranes to measure how these thermodynamic properties vary during the various stages of an actual process of membrane division. This will allow them to test whether ring formation and contraction in a cell-like geometry is energetically favorable compared to a non-contracting steady state.  The proposed experiments will quantify the thermodynamics of the actomyosin cytoskeletal system at the heart of cell division, and in doing so make an important contribution to an emerging body of knowledge about cellular thermodynamics.