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.

The International Congress of Mathematicians (ICM) is where mathematicians come to present groundbreaking research and to receive the highest honors in the field, including the Fields Medals. Held every four years, this flagship event will return to an in-person format in July 2026, when it will be based in Philadelphia. This is the first time in four decades that the United States has hosted the ICM. Over 6,000 participants are expected. With philanthropic funding from Sloan and other foundations, the American Mathematical Society will ensure broad global representation by providing travel support to 658 mathematicians who, because they come from under-resourced  communities and countries, would not be able to attend otherwise. Outreach plans include mathematical exhibits and events designed for the public generally and for young people in particular. By lowering barriers to participation, this grant will enable broader engagement with mathematics and with mathematicians from around the world. 

Funds from this grant support research by Patrick Oakes and Jordan Beach, both Professors in the Department of Cell and Molecular Physiology at Loyola University Chicago, to better understand how a cell’s energy supply is linked to the mechanical forces it generates—an important gap in our understanding of how cells regulate energy resources to coordinate basic functions such as movement, division, and changes in shape. Oakes, Beach, and their team will use Sloan funding to measure how cellular ATP levels (the primary form of usable energy in cells) relate to force generation by the actomyosin cytoskeleton, an intracellular protein network that drives contraction and is a key player in cell division and motion. The work will be done using live cells, with experiments that both increase and decrease ATP  availability to see how the actomyosin skeleton responds, as well as with experiments that stimulate cytoskeletal activity to see how cellular ATP levels and other major energy-consuming processes respond. The project will also examine these relationships at finer spatial scales inside cells. Using imaging-based metabolic sensors and force-measurement methods, the research team will map and quantify where ATP is higher or lower inside the cell and compare those patterns with where contractile forces are generated. They will also field a series of experiments where ATP levels are manipulated in localized regions while observing the behavior of the corresponding section of the cytoskeletal network. If successful, the project will produce quantitative measurements describing how cellular energy availability and mechanical force generation influence one another at both whole-cell and subcellular scales, along with datasets and analysis that can help clarify how cells regulate mechanical behavior.