Cells switch From Healthy to Diseased States in a Sudden Shift

New research digs into how cells collectively switch from healthy to disease states.

Cells convert mechanical forces into signals that influence physiological processes, such as exercise strengthening bones.

the research team at Washington University in St. Louis and Tsinghua university in Beijing have discovered that biological tissues can also undergo dramatic phase transitions, or collective shifts where wound healing cells can switch from disordered, healthy states to highly coordinated disease states, like when water suddenly freezes into ice.

This revelation, published in Proceedings of the National Academy of Sciences, reveals why fibrotic diseases often progress in switch-like jumps rather than gradually and points to new therapeutic strategies that target the physical properties of tissue rather than just cellular biochemistry.

The team used computational modeling to uncover the mechanical “tipping point” that determines whether cells can collectively coordinate to spread a disease called fibrosis, an excessive scarring that underlies failure of nearly any organ, and especially in diseases of the liver, lungs, kidneys, and heart.

“What we’ve shown is that this isn’t a gradual process,” explained Guy M. Genin, co-senior author and a professor of mechanical engineering in the McKelvey School of Engineering at WashU.

“Ther’s a sharp transition point. When cells are within a critical spacing that depends on the way their matrix deforms, thay can ‘talk’ to each other mechanically through the matrix. Above it, they’re effectively isolated, and below it they interact strongly with one another. This on-off switch behavior is what we see in fibrosis progression: periods of stability followed by rapid scarring.”

Phase transitions are familiar in physics: Water freezes to ice at 0 C, and iron becomes ferromagnetic below 770 C. The new research demonstrates that living tissues show similar behavior. When cells are spaced far apart in a tissue, they act independently, but when cell density crosses a critical threshold-a few hundred micrometers-they begin to coordinate their behavior.