What stiffening lung tissue reveals about the earliest stages of fibrosis

Fibrosis of the lungs is often a silent disease until it’s too late. By the time patients are diagnosed, the scarring of their lung tissue is already advanced, and current treatments offer little more than a slowing of the inevitable.

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That’s the question Claudia Loebel, Reliance Industries Term Assistant Professor in bioengineering at Penn’s School of Engineering and Applied Science, and Donia Ahmed, a doctoral student in Loebel’s lab, set out to understand the very first steps of this disease before irreversible damage sets in. Their Nature Materials paper explores how subtle changes in the mechanical environment of lung tissue might set off the chain reaction that leads to fibrosis.

“Once it’s diagnosed, patients only have two FDA-approved drugs, and both just slow down the disease. They don’t stop it or reverse it,” says Loebel. “What’s worse is that we often don’t know what caused it in the first place, so we also don’t have a clear idea of how to prevent it.”

Much of the research to date has focused on the later stages of the disease, when tissue has already stiffened and scarred. Loebel and Ahmed examined what happens right at the onset. Specifically, they looked at how tissue stiffness alone might influence cell behavior in the lungs, offering a new window into fibrosis as it unfolds.

Using a technique called photochemical cross-linking, the researchers exposed lung tissue to blue light, which triggered the extracellular matrix—the fibrous scaffolding surrounding cells—to stiffen. Unlike traditional ultraviolet light, blue light is gentler on living cells, making it ideal for studying live tissue. With these flashes of blue light, the team was able to localize the stiffening of tissue in both healthy mouse and human lung tissue.

As the tissue stiffened under the light, Ahmed observed that cells began to stretch out, changing shape—and it wasn’t just cosmetic. This physical stretching was a sign that the cells were transitioning into a different cell type—but then they stalled.

Loebel and Ahmed’s model suggests that changes in tissue stiffness alone can prompt cells to begin transitioning, and when they get stuck, they contribute to the very stiffness that triggered them—setting up a potential feedback loop that accelerates disease.

Read more at Penn Engineering Today.