Key points for students use physics to understand how cells sort themselves – Syracuse University News

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

Erin McCarthy ’23, summa cum laude in physics, is a rarity among young scientists. As an undergraduate researcher in the Department of Physics in the College of Arts and Sciences, she led a study that appeared in Physical Review Letters in March 2024. 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 an article in Physical Review Letters,” says co-author M. Lisa Manning and William R. Kenan, Jr. professor of physics, and also founder and director of the BioInspired Institute. “Your scientific colleagues must judge it as exceptional.”

McCarthy, a New Jersey native, chose Syracuse because of its “tremendous energy,” she says. “The educational and research side were great. I planned to be a physics major with a degree. I loved physics and biology, and I wanted to be involved in healthcare and medicine. And I was lucky enough to meet Dr. Manning as a freshman, and she introduced me to computational biophysics. I started doing research during my freshman year, which is very unusual.”

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

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

The research team used computational physics models to discover the underlying mechanisms that ensure that particles are spontaneously classified into different groups.

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

For example, in the early stages of an embryo, cells start out in heterogeneous mixtures. Cells must sort themselves into different compartments to form separate homogeneous tissues. This is one of the most important collective cell behaviors at work during tissue and organ development and organ regeneration.

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

Previous physics research has shown that particles disintegrate when some receive a higher temperature shock. When one population of particles is injected with energy on a small scale, it becomes active – or ‘hot’ – while the other population remains inactive or ‘cold’. This heat difference causes a reorganization between 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 up more space,” says co-author Manna. “But that only happens if a gap is created between the particles.”

Previous modeling identified the behavior of self-sorting particles at less packed, intermediate densities.

But the Syracuse team discovered something surprising. After injecting energy into a population of high-density particles, the hot particles didn’t push the cold particles around. The hot particles had no room for that.

This is important because biological particles – proteins in cells and cells in tissue – usually live in tight, crowded spaces.

“For example, your skin is a very dense environment,” says McCarthy. “Cells are so close together that there is no space between them. If we want to apply these physics findings to biology, we need to look at high densities before our models are 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 doesn’t always separate things, so you can’t use it in biology,” says Manning. ‘You have to look for another mechanism.’

For Manning, this study illustrates the strengths of Syracuse University. “The fact that a student led this research speaks to the awesome quality of the students we have at Syracuse University, who are as good as any anywhere in the world, and to the exceptionalism of Erin herself,” said Manning.

Manna, the postdoctoral mentor for the final part of McCarthy’s project, was essential in bringing it to fruition.

“Without him, the investigation wouldn’t have happened,” Manning said. “This shows that we can recruit excellent postdoctoral fellows to Syracuse because we are such a great research university.” Manna is now a postdoctoral researcher in the Department of Physics at Northeastern University.

McCarthy, a research technologist in a biological laboratory at Northwestern University School of Medicine, plans to apply to graduate school.

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

Story by John H. Tibbetts