As tissue changes shape—a wound healing, say, or an embryo growing—the cells slide alongside each other, elongating and behaving in a fluid-like manner at the microscopic level. But in certain contexts, such as cancer metastasis, inhibiting that tissue fluidity could be useful to stop the disease from spreading.
The first step is better understanding how cells move within a tissue. In a paper published in the journal Nature Communications, University of Wisconsin-Madison mechanical engineering researchers and collaborators at Northeastern University reveal new details about the mechanisms behind tissue fluidity—fundamental work that could inform therapeutic approaches in future decades.
“There are tons of processes in the human body that involve cellular forces, cellular shape and cellular motion: The development of tissues, healing of tissues, invasion of cancer,” says Jacob Notbohm, the Harvey D. Spangler associate professor in the Department of Mechanical Engineering at UW-Madison. “All of these, in some way, are related to forces that cells transmit to their surroundings, and then in turn how the surroundings deform.”
The work, led by Notbohm and postdoctoral researcher Pradip Bera, augments existing mathematical models of how tissue fluidity works in epithelial cell monolayers, the outer layers of tissues that line organs and surfaces within the body. Whereas the previous understanding focused on the link between the physical shape of cells and fluidity, the Notbohm group’s experiments uncovered that cell-to-cell adhesion caused a drag force that resisted motion.
“Resistance is there,” says Notbohm. “It’s important—and in some cases, it’s way, way more important than the shape description that had been used for the past decade.”
Notbohm first met collaborator Dapeng Bi, an associate professor of physics at Northeastern who led the modeling portion of the work, more than a decade ago. Their conversation planted the seeds for this research project.
While further investigation could uncover more clues that could point toward strategies for manipulating cellular behavior—to speed wound healing, for example—Notbohm says part of the beauty of basic science is its unforeseen consequences.
“To me, what’s most exciting about the type of work we do, the fundamental work, is there’s going to be new ideas created as a result of this work,” he says. “This is laying the groundwork for technological innovation and human health interventions that we can’t even conceive of today. Because of the knowledge base we’re creating, a generation from now, people will be able to use that knowledge to create new ideas.”
This research was supported by the National Science Foundation (grants CMMI-2205141, DMR-2046683 and PHY-2019745), the National Institutes of Health (grants R35GM151171 and R35GM150494), the Sloan Research Fellowship and the Human Frontier Science Program (grant RGP0007/2022).
Molly McCord (MS ’24, PhD in biophysics ’26), an alumna of the Notbohm lab and current postdoctoral fellow at the Morgridge Institute for Research, was also an author on the paper.
Top photo caption: Postdoctoral researcher Pradip Bera, left, and Associate Professor Jacob Notbohm. Photo: Tom Ziemer