A&S physicists develop one of the first models to capture the dynamics of movement of confined cells

The process of normal cell division in the human body is quite simple: start dividing in response to a signal, such as injury, and stop when enough cells have been produced and the skin is scarred. But cancer cells ignore stop signs. They grow and spread quickly, proliferating even in tight spaces.

Vimentin (green) protein helps protect a cell’s nucleus and DNA during migration. (Image courtesy of Maxx Swoger)

Similar to navigating through a large crowd of people, moving through dense tissue is no easy task. Any normal cell would die in the process, but many cancer cells have a cage-like protein that helps them protect their nucleus and DNA. This protein, called vimentin, is often expressed in intermediate filaments (one of the three building blocks of the cell) during cell movement. And now researchers at the College of Arts and Sciences are learning more about this protein, which could potentially help with cancer treatment or wound healing.

In the past, the role of vimentin remained largely unclear, but researchers at the college developed one of the first models that capture the dynamics of confined cell motility and show how vimentin helps protect the cell nucleus for the migration. The team, which includes lead author Sarthak Gupta, a graduate student in physics; Alison Patteson, assistant professor of physics; and Jennifer Schwarz, professor of physics, recently published their findings in the New Journal of Physics. Their model sheds light on the function of a protein that is a major player in cancer growth, and their results could one day help researchers determine better ways to stop the spread of cancer.

Cell migration is a fundamental process that helps build and maintain tissue. During wound healing and cancer metastases, two cases where cells are known to be on the move, they depend on the cell’s skeleton, called the cytoskeleton, to protect itself and generate strength. The cytoskeleton is made up of a network of proteins, and one in particular, vimentin, is often present when cells decide to travel.

“When a cell is stationary, we know that the expression of the vimentin protein is very minimal,” Gupta explains. “Conversely, when cells become migratory, the expression of this protein increases.”

In Patteson’s lab, researchers recreated what a cell goes through as it migrates to observe the role of vimentin in the process. By squeezing cells with and without vimentin through narrow microchannels on collagen gels, they mimic in 3D how cells navigate through small pores in real tissue. In their observations, they found that the presence of vimentin in the cytoskeleton was crucial for the survival of cells moving in 3D space, which the researchers were previously unable to detect using traditional two-dimensional experiments on blood. glass or plastic.

Using the experimental results of Patteson, Gupta and Schwarz developed a model that captures the effects of the vimentin protein on the cytoskeleton and nucleus of the cell. This model allows the team to regulate cell-generated forces and nucleus stiffness, providing visual evidence of Patteson’s lab experiments.

“Without vimentin, we found that the cells are very soft and the nucleus deforms as it moves,” Gupta explains. “In the simulation with vimentin, the cell is much more resistant to deformation and the interior of the nucleus and its DNA are protected.”

Understanding the role of vimentin in protecting cancer cells as they spread throughout the body, Patteson says their research could help identify drugs that could slow its growth.

“In theory, treating cancer with drugs targeting vimentin might be an option,” says Patteson. “By targeting vimentin, the cell will not be able to move efficiently from one place to another, thus stopping the spread of cancer.”

The team says another possible application could be in wound healing, where drugs that stimulate vimentin expression could be administered to speed up the movement of cells to the wound area, essentially speeding up the restoration process. fabrics.

Read the team’s full article in the New Journal of Physics.

The funding that has contributed to their work includes a grant from the National Science Foundation-Division of Materials Research and an Isaac Newton Prize from the Department of Defense owned by Schwarz; a National Institutes of Health Maximizing Investigator Fellowship owned by Patteson; a Syracuse University graduate scholarship awarded to Gupta; and a CUSE grant from Syracuse University and a Syracuse BioInspired grant awarded to Patteson and Schwarz.

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