Syracuse Sun

How do cells take the shape they do and perform their functions? The enzymes and molecules that make them up are not themselves living, yet they adapt to their environment, come together, interact, and ultimately create life. Understanding this process involves significant questions crucial for new biotechnologies and other advancements.

The Alfred P. Sloan Foundation, a private nonprofit grantmaking organization, initiated its Matter to Life program to address some of these questions. The program aims "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."

As part of this initiative, Jennifer Ross and Jennifer Schwarz, professors in the Department of Physics in the College of Arts and Sciences and members of the BioInspired Institute, received a three-year grant. Their research will explore a fundamental unanswered question about cell functionality and the energy and entropy landscape within cell interiors.

"There is a lack of quantitative understanding of the principles governing the non-equilibrium control knobs inside the cell," Ross and Schwarz explained in their proposal. "Without this knowledge, we will never understand how cells work or how we can replicate them in synthetic materials systems."

Their focus is on protein condensates within cells, specifically their liquid-liquid phase separation. This phenomenon is described as the "killer app" for sculpting energy and entropy in cells.

"Liquid-liquid phase separation is when two liquids separate, like oil and water," Ross says. "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."

They aim to understand how cells self-organize without a membrane acting as a containment system and how they react to their environment.

"This droplet formation is so sensitive to temperature and its surroundings," says Schwarz. "The cell knows, 'A ha!' The temperature is increasing, so the environment is slightly different. So…I’m going to adapt."

Ross will serve as principal investigator with graduate student assistance performing reconstitution experiments. Co-principal investigator Schwarz's team will delve into theoretical science using predictive simulations. The grant also funds a paid undergraduate student and two local high school students through summer programs.

The goal is that understanding cell behavior at this level could lead to breakthroughs in developing smart synthetic materials. "Imagine a road-paving material that could identify when a pothole develops and heal itself," Ross says.

This research exemplifies numerous possibilities for learning from biological systems.

Story by Laura Wallis