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STEM

Undergraduate Spearheads Study Using Physics to Understand How Cells Self-Sort

Sunday, April 21, 2024, By News Staff
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alumniBioInspiredCollege of Arts and SciencesResearch and Creativestudent
two people standing in front of research poster

Physics alumna Erin McCarthy ’23, right, was lead author on a study published in Physical Review Letters, which uncovered mechanisms that cause particles to sort spontaneously into different groups. Professor M. Lisa Manning, left, was a co-author.

Erin McCarthy ’23, physics summa cum laude, is a rarity among young scientists. As an undergraduate researcher in the College of Arts and Sciences’ Department of Physics, she guided a study that appeared in March 2024 in Physical Review Letters. It is the most-cited physics letters journal and the eighth-most cited journal in science overall.

McCarthy and postdoctoral associates Raj Kumar Manna and Ojan Damavandi developed a model that identified an unexpected collective behavior among computational particles with implications for future basic medical research and bioengineering.

“It’s very difficult to get a paper into Physical Review Letters,” says M. Lisa Manning, co-author and the William R. Kenan, Jr. Professor of Physics, as well as founding director of the BioInspired Institute. “Your scientific peers must judge it as exceptional.”

McCarthy, a New Jersey native, chose Syracuse because of its “tremendous energy,” she says. “The educational and the research side of things was amazing. I came planning to be a physics major who was premed. I loved physics and biology, and I wanted to be involved in healthcare and medicine. And I got lucky in that I met Dr. Manning as a freshman, and she introduced me to computational biophysics. I started in research during my freshman year, which is extremely unusual.”

“Erin learned coding from scratch, and then did hours and hours of simulations, which took a lot of perseverance,” says Manning. “It’s just a fantastic testament to her work ethic and brilliance that this paper appeared in such a prestigious journal.”

person standing outside Physics Building

Erin McCarthy standing in front of the Physics Building during 2023 graduation weekend.

The research team used computational physics modeling to figure out the underlying mechanisms that cause particles to sort spontaneously into different groups.

Learning how particles behave in physics models could provide insight into how living biological particles—cells, proteins and enzymes—remix themselves in development.

In the early stages of an embryo, for example, cells start out in heterogeneous mixtures. Cells must self-sort into different compartments to form distinct homogenous tissues. This is one of the major collective cell behaviors at work during development of tissues and organs and organ regeneration.

“Cells need to be able to organize themselves properly, segregating themselves to do their jobs,” says McCarthy. “We wanted to understand, if you remove chemistry and look strictly at physics, what are the mechanisms by which this reorganization can happen spontaneously?”

Previous physics investigations found that particles separate when some receive a jolt of higher temperature. As one population of particles becomes injected with energy at a small scale, it turns active—or “hot”—while the other population is left inactive, or “cold.” This difference in heat causes a reorganization among the two populations. These models are simplified versions of biological systems, using temperature to approximate cellular energy and movement.

“Hot particles push the cold particles aside so they can take over a larger space,” says co-author Manna. “But that only happens when a gap exists between particles.”

Previous modeling identified self-sorting particle behavior at less-packed, intermediate densities.

But the Syracuse team found something surprising. After injecting energy into a population of high-density particles, the hot particles did not shove cold ones around. The hot particles lacked space to do so.

That is important because biological particles—proteins in cells and cells in tissue—typically live in tight, crowded spaces.

“Your skin, for instance, is a very dense environment,” says McCarthy. “Cells are packed so closely together, there’s no space between them. If we want to apply these physics findings to biology, we must look at high densities for our models to be applicable. But at very high densities, the difference in activity between two populations does not cause them to sort.”

There must be some other self-sorting mechanism at play in biology. “Temperature or active injection of energy does not always separate things, so you can’t use it in biology,” says Manning. “You must search for some other mechanism.”

To Manning, this study illustrates the strengths of Syracuse University. “The fact that an undergraduate spearheaded this research speaks to the awesome quality of students we have at Syracuse University, who are as good as those anywhere in the world, and to the exceptionalness of Erin herself,” says Manning.

Manna, the postdoctoral mentor for the last part of McCarthy’s project, was essential in driving it to conclusion.

“The study wouldn’t have happened without him,” says Manning. “This demonstrates that we are able to recruit outstanding postdoctoral associates to Syracuse because we are such a great research university.” Manna is now a postdoctoral fellow in the Department of Physics at Northeastern University.

McCarthy, a research technologist in a biological lab at the Northwestern University School of Medicine, plans to start applying for graduate school.

“At Syracuse,” says McCarthy, “I learned how much I love research and want it to be a part of my future.”

Story by John H. Tibbetts

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