What does the fairy tale of the princess and the pea have to teach us about our cells?
Amit Pathak, professor of mechanical engineer and materials science at Washington University in St. Louis, feels the way through the research.
Amit Pathak is a Professor of Mechanical Engineering & Materials Science at Washington University in St. Louis. His research focuses on mechanobiology, exploring how cells sense and respond to mechanical properties of their environment, with applications in cancer metastasis, wound healing, and tissue engineering.
While diseases are traditionally defined by genetic alterations in cells, our bodies undergo mechanical changes as well. In my lab, we study mechanobiology, which asks: how do cells respond to the physical world around them?
Over the last two decades, scientists have learned that cells aren’t just passive blobs. They actually sense the stiffness of the surfaces they stick to. This sensing—called mechanotransduction—guides how cells move, grow, and even turn into diseased versions of themselves.
In a recent study, we found something surprising. Groups of epithelial cells—the kind that line your organs—can feel through layers of fibrous collagen up to 100 microns deep. It’s a bit like the fairy tale of the princess and the pea. She could feel a tiny pea under a pile of mattresses. In real life, it’s like the difference between sleeping on a mattress on the floor versus one on a bed frame—you feel the support differently. The epithelial cell clusters in our experiments did something similar: they push and pull on their surroundings to “feel” what’s beneath. Depending on the stiffness of their distant layers, which could be soft tissue, a hard tumor, or bone in the body, cells change how they move. This is an emergent property of cell collectives, because single cells can only sense a few microns deep.
Based on this work, we suspect there may be specific regulatory proteins that help cells sense distant, disease-like environments—ones we may have overlooked. This kind of long-distance sensing could reveal new targets for cancer therapy.
That’s the core mission of my lab: to understand whether and how cells can sense distant environments—ones they’ve encountered before, or ones they’re moving toward. If true, this could mean that mechanical memory shapes how cancer spreads or how healthy cells respond to nearby tumors.
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