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The narrative of the princess and the pea conjures up an image of a remarkably sensitive royal young lady so cultured, she can detect a pea beneath a pile of mattresses. In terms of human biology, it similarly requires an unusual individual to perceive well beyond its surroundings, in this instance, a cancer cell. Presently, scientists also recognize that typical cells can execute a comparable feat by collaborating.
Research published in the journal PNAS by engineers at Washington University in St. Louis provides a more precise understanding of how cells can sense beyond their immediate environment. This study can enhance knowledge regarding cancer migration and highlight potential targets to inhibit that movement.
Amit Pathak, a professor of mechanical engineering and materials science at the McKelvey School of Engineering, elucidated that “depth mechano-sensing” refers to how cells are capable of sensing beyond what they are attached to. Through previous investigations, he and his colleagues recognized that abnormal cells with a “high front-rear polarity” (a sign of migrating cells) can sense up to 10 microns beyond their adhered environment.
A portion of that sensory capability pertains to how the cell alters the surrounding fibrous collagen to extend into the extracellular matrix (ECM) and “detect” the next layer, whether it is a hard tumor, soft tissue, or bone just around the corner. The individual abnormal cell can “perceive” the stiffness of the ECM and determine its path based on that information.
The latest research indicates that a group of epithelial cells, located on the surface of tissue, can achieve the same, collaborating to generate sufficient force to “sense” through the fibrous collagen layers as far as 100 microns away.
“Because it’s a collective of cells, they produce greater forces,” remarked Pathak, who co-authored the study along with PhD student Hongsheng Yu.
Their models suggest that this happens in two distinct stages of cell clustering and migration. The sensations the clustered cells experience will influence their movement and dispersal.
The enhanced sensing ability of cancer cells implies that they can exit the tumor environment and elude detection, migrating freely due to their superior awareness of what lies ahead, even in a soft medium. The researchers’ forthcoming step is to comprehend the underlying mechanisms and whether specific regulators allow for this range. These regulators may serve as potential targets for cancer treatment. If a cancer cell cannot “detect” its way forward, its harmful spread might be curtailed.
This article initially appeared on the McKelvey School of Engineering website.
Hongsheng Y, Pathak A. Emergent depth-mechanosensing of epithelial collectives regulates cell clustering and dispersal on layered matrices. PNAS, Sept. 11, 2025. DOI:
https://doi.org/10.1073/pnas.2423875122
Funding for this research was provided by the National Institutes of Health (NIH) (R35GM128764) and the National Science Foundation, Civil, Mechanical and Manufacturing Innovation (2209684).
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