Engineers at Washington University in St. Louis report that while single abnormal cells can mechanically probe roughly 10 microns beyond what they directly touch, groups of epithelial cells can combine forces through collagen to sense features more than 100 microns away—an effect the researchers say could help explain how cancer cells navigate tissue.
Researchers at Washington University in St. Louis say they have identified a form of long-range mechanical sensing that allows cells to detect features far beyond the surfaces they are physically attached to.
The study—led by Amit Pathak, a professor of mechanical engineering and materials science at the university’s McKelvey School of Engineering, with PhD student Hongsheng Yu as a co-author—was published in Proceedings of the National Academy of Sciences in 2025.
How far cells can “feel”
According to the researchers, prior work from the group showed that single abnormal cells with “high front-rear polarity,” a trait associated with migrating cells, can detect physical cues up to about 10 microns beyond their immediate point of attachment. They do this by pulling on and deforming surrounding collagen fibers in the extracellular matrix, which can transmit information about what lies ahead.
In the new work, the team reports that epithelial cells—cells that line surfaces of many tissues—can extend that sensing range dramatically when they move and deform collagen as a collective. Using a collagen–polyacrylamide double-layer hydrogel system, the researchers found that epithelial cell collectives could mechanosense an underlying “basal” substrate at depths greater than 100 microns, as measured through cell clustering behavior and collagen deformation.
“Because it’s a collective of cells, they are generating higher forces,” Pathak said in a university release describing the research.
Modeling suggests a two-stage process
The researchers also used computational modeling to examine how collective forces translate into long-range sensing. The model described the behavior as unfolding in two broad stages: an initial phase of cell clustering accompanied by dynamic collagen deformation, followed by a phase of cell migration and dispersal.
In the experiments described in the paper’s abstract, stiffer underlying substrates were associated with higher collagen deformation and stiffening and with reduced dispersal of epithelial clusters.
Why it matters for cancer research
In a summary released by the university, the researchers suggest that the ability to detect what lies ahead could help cancer cells escape a tumor and navigate surrounding tissue. The release argues that understanding how sensing range is controlled could point to strategies aimed at disrupting a cancer cell’s ability to “feel” its path, potentially limiting migration.
The work was supported by the National Institutes of Health under grant R35GM128764 and the National Science Foundation’s Civil, Mechanical and Manufacturing Innovation program under grant 2209684.
