In the fairy tale of The Princess and the Pea, there is a story about a young royal who was so sensitive that he was able to find a small pea hidden under many mattresses. Something similar happens in biology when cells sense conditions far beyond what they are directly in contact with. Until recently, this remarkable ability was primarily associated with abnormal cells, such as cancer cells. New research shows that ordinary cells can accomplish similar feats by working together.
Engineers from Washington University in St. Louis report their findings in a magazine PNAS. Their research reveals how cells sense and respond to their environment beyond the surfaces to which they attach. Understanding this process can help scientists learn more about how cancer cells move through the body and may reveal new ways to slow or prevent the spread of cancer.
How long-distance cell sensing works
Amit Pathak, a professor of mechanical engineering and materials science in the McKelvey School of Engineering, studies how cells interact with the physical properties of their surroundings. He explained that “depth mechanical sensing” describes a process that allows cells to detect features beyond the surface they are attached to.
Previous research by Pathak et al. found that abnormal cells with “high anteroposterior polarity” (indicative of migratory cells) have an especially strong ability to sense their environment. These cells can detect physical cues up to 10 microns beyond the area to which they are attached.
This sensing ability depends in part on how the cells pull and reform the surrounding fibrillar collagen. By deforming these fibers, cells can extend their reach into the extracellular matrix (ECM) and “feel” what’s in the next layer. The next layer could be something hard, such as a tumor, soft tissue, or even nearby bone. By detecting the stiffness of the ECM, the direction in which a single abnormal cell migrates can be determined.
Expanding the sensing range with the power of collective cells
New research shows that a group of epithelial cells that form the surface of many tissues can achieve even wider sensing ranges. Working together, these cells generate enough force to probe the fibrillar collagen and detect layers as far as 100 microns apart.
“Because it’s a collection of cells, it generates higher forces,” said Pathak, who worked with doctoral student Hongsheng Yu.
Computer models suggest that this process unfolds in two stages, as cells come together and begin to migrate. During these stages, the information that cells gather about their surroundings influences how they move and spread.
Implications for understanding the spread of cancer
Cancer cells appear to benefit from this enhanced sensing ability. The ability to detect what’s in front of you helps you escape the tumor environment and pass through the surrounding tissue while avoiding detection. This ability allows them to move more easily in softer environments.
Researchers now want to understand exactly how this sensing range is controlled, and whether specific regulators determine how far into the cell’s surroundings it can sense. Identification of these regulatory factors may open the door to new cancer treatments. If scientists can interfere with a cancer cell’s ability to “sense” where it’s going, it could limit the spread of the disease.
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).
