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The fairy tale of the princess and the pea tells of a young royal so sensitive she could detect a tiny pea hidden beneath many mattresses. In biology, something similar happens when a cell senses conditions far beyond what it directly touches. Until recently, this remarkable ability was mostly linked to unusual cells such as cancer cells. New research shows that ordinary cells can achieve a similar feat when they work together.
Engineers at Washington University in St. Louis reported their findings in the journal PNAS. Their work sheds light on how cells detect and respond to their environment beyond the surface they attach to. Understanding this process could help scientists learn more about how cancer cells move through the body and may reveal new ways to slow or prevent that spread.
The Mechanics of Long Range Cell Sensing
Amit Pathak, a professor of mechanical engineering and materials science at the McKelvey School of Engineering, studies how cells interact with the physical properties of their surroundings. He explained that “depth mechano-sensing” describes the process that allows cells to detect features beyond the surface they are attached to.
In earlier studies, Pathak and his colleagues found that abnormal cells with a “high front-rear polarity” (indicative of migrating cells) have an especially strong ability to sense their environment. These cells can detect physical cues up to 10 microns beyond the area where they are attached.
This sensing ability relies partly on how a cell pulls and reshapes the fibrous collagen around it. By deforming these fibers, the cell extends its reach into extracellular matrix (ECM) and can “feel” what lies in the next layer. That next layer could be something stiff such as a tumor, softer tissue, or even bone nearby. By detecting the stiffness of the ECM, a single abnormal cell can determine the direction it should move.
Collective Cell Forces Extend the Sensing Range
The new research shows that groups of epithelial cells, which form the surfaces of many tissues, can achieve an even greater sensing range. When these cells act together, they generate enough force to probe through the fibrous collagen and detect layers as far as 100 microns away.
“Because it’s a collective of cells, they are generating higher forces,” said Pathak, who conducted the research with PhD student Hongsheng Yu.
Computer models suggest that this process unfolds in two stages as cells cluster together and begin migrating. During these phases, the information the cells gather about their surroundings influences how they move and spread.
Implications for Understanding Cancer Spread
Cancer cells appear to benefit from this enhanced sensing ability. Their capacity to detect what lies ahead helps them escape the tumor environment and move through surrounding tissue while avoiding detection. This ability allows them to migrate more easily, even in softer environments.
Researchers now want to determine exactly how this sensing range is controlled and whether specific regulators determine how far cells can detect their surroundings. Identifying those regulators could open the door to new cancer treatments. If scientists can disrupt a cancer cell’s ability to “feel” its path forward, they may be able to limit how far the disease spreads.
Funding for this research was provided by the National Institutes of Health (NIH) (R35GM128764) and National Science Foundation, Civil, Mechanical and Manufacturing Innovation (2209684).
