In living systems, the orchestration of shape, function, and adaptation emerges from components that are not themselves alive. Proteins, enzymes, and other molecules interact within a cell’s crowded interior, responding to environmental cues and reorganizing in ways that sustain life. Understanding the physical principles behind this behavior remains one of the most compelling challenges in modern science, with implications for biotechnology and advanced materials engineering.
The Alfred P. Sloan Foundation has launched its Matter to Life program to address these questions. The initiative’s stated aim is “To sharpen our scientific understanding of the physical principles and mechanisms that distinguish living systems from inanimate matter, and to explore the conditions under which physical principles and mechanisms guide the complexification of matter towards life.”
Among the program’s recent awardees are Jennifer Ross and Jennifer Schwarz, professors in the Department of Physics at the College of Arts and Sciences and members of the BioInspired Institute. Their three-year grant targets what they describe as a fundamental unanswered question: how the energy and entropy landscape inside cells governs their functionality.
“There is a lack of quantitative understanding of the principles governing the non-equilibrium control knobs inside the cell,” Ross and Schwarz stated in their proposal. “Without this knowledge, we will never understand how cells work, or how we can replicate them in synthetic materials systems.”
Their research zeroes in on protein condensates—clusters of proteins within cells—and the phenomenon of liquid-liquid phase separation. Ross calls this separation the “killer app” for shaping energy and entropy inside cells. “Liquid-liquid phase separation is when two liquids separate, like oil and water,” she explains. “The proteins separate out [into droplets] and make what we think of as membrane-less organelles. We’re interested in how both energy-using systems and entropy-controlling systems can help to shape those organelles.”
Unlike membrane-bound structures, these droplets self-organize without a physical barrier. Schwarz emphasizes their responsiveness: “This droplet formation is so sensitive to temperature and its surroundings. The cell knows, ‘A ha!’ The temperature is increasing, so the environment is slightly different. So…I’m going to adapt.”
Ross, serving as principal investigator, will lead experimental reconstitution studies to recreate and observe these processes in controlled settings. Schwarz, as co-principal investigator, will focus on theoretical modeling, using predictive simulations to map how energy and entropy parameters influence droplet behavior. Graduate students will assist in both tracks, while the grant also supports a paid undergraduate researcher and two local high school students through summer programs.
The work sits at the intersection of biophysics and materials science. In engineering contexts, the principles uncovered could inform the design of synthetic systems that mimic cellular adaptability. Materials capable of sensing and responding to damage, for example, could transform infrastructure maintenance. Ross offers a tangible vision: “Imagine a road-paving material that could identify when a pothole develops and heal itself.”
Liquid-liquid phase separation is already recognized in polymer science and colloidal chemistry, but the cellular version operates under far more complex, non-equilibrium conditions. In cells, molecular crowding, active transport, and localized energy inputs create dynamic environments where droplets can assemble, dissolve, or change composition in response to minute shifts. For engineers, decoding these control mechanisms could open pathways to self-healing composites, adaptive coatings, or responsive aerospace components.
The integration of experimental and theoretical approaches in this project reflects a broader trend in advanced materials research: coupling direct observation with high-fidelity simulation to accelerate discovery. Predictive models can guide experiments toward the most promising parameter spaces, while empirical data refine those models for greater accuracy.
By probing how living matter organizes itself without external management, Ross and Schwarz aim to uncover rules that could be applied far beyond biology. The potential to engineer matter that autonomously adapts to stress, temperature changes, or mechanical wear could reshape multiple industries, from transportation to robotics.