Tissue 'tipping points': How cells collectively switch from healthy to disease states

Cells convert mechanical forces into signals that influence physiological processes, such as exercise strengthening bones. A research team has 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 discovery, published Oct. 3, 2025, 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 they have shown is that this isn't a gradual process.

There's a sharp transition point. When cells are within a critical spacing that depends on the way their matrix deforms, they 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 apart—they begin communicating mechanically and acting in concert, dramatically compacting and stiffening the tissue.

The research shows why this phase transition occurs: Fibrous networks like collagen enable long-range mechanical communication in a way that uniform elastic materials cannot.

Collagen fibers can be recruited and aligned by cell forces, creating stiffened 'tension bands' that act as mechanical communication highways, transmitting signals over much longer distances.

The critical factor is what the researchers call the "critical stretch ratio," which is how much the collagen must be stretched before individual fibers align and stiffen. This property is determined by collagen crosslinking, which increases with aging and is influenced by factors like diet, advanced glycation end products, and metabolic diseases like diabetes.

 Xiangjun Peng et al, Fiber recruitment drives a phase transition of cell polarization at a critical cell spacing in matrix-mediated tissue remodeling, Proceedings of the National Academy of Sciences (2025). DOI: 10.1073/pnas.2514995122

'Rotten egg' gas could be the answer to treating nail infections, say scientists

Hydrogen sulfide, the volcanic gas that smells of rotten eggs, could be used in a new treatment for tricky nail infections that acts faster and with fewer side effects, according to scientists.

Hydrogen sulfide (H2S) demonstrates strong antimicrobial activity against a range of nail pathogens, including drug-resistant fungi, and penetrates the nail plate more effectively than current topical treatments. Laboratory results indicate it disrupts microbial energy production, causing irreversible damage. A topically applied H2S treatment may offer a faster, safer alternative for nail infections.

Nail infections are mostly caused by fungi and occasionally by bacteria. They are very common, affecting between 4 and 10% of the global population, rising to nearly half those aged 70 or over. These infections can lead to complications, particularly in vulnerable groups such as diabetics and the elderly, but are notoriously difficult to treat.
Current treatments include oral antifungals taken in pill form, and topical treatments applied directly to the nail. Oral antifungals take around 2–4 months to act and are reasonably effective, but they carry risks of side effects, especially in patients with other medical conditions.

Treatments applied directly to the nail are safer, but they often take much longer to work, sometimes taking even years to work, and they frequently relapse or fail. This is largely because it's very difficult to get the drug to penetrate through the nail to where the infection resides.

Even the most effective topical treatments have relatively low cure rates, so there is a clear need for new therapeutic approaches that are safe, effective, and capable of reaching microbes embedded deep within the nail.
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A research team has now found that hydrogen sulfide (H₂S), a small, naturally occurring gas, could be developed into a promising new treatment.
Previous work has shown that it penetrates the nail plate far more efficiently than existing topical drugs, and now the team has demonstrated that it has strong antimicrobial activity against a wide range of nail pathogens, including fungi that are resistant to common antifungal treatments.

In laboratory tests, the team used a chemical that breaks down to release the hydrogen sulfide gas and found that it acts in a unique way, disrupting microbial energy production and triggering irreversible damage, ultimately killing the fungi.

Fritz Ka-Ho Ho et al, Antimicrobial effects and mechanisms of hydrogen sulphide against nail pathogens, Scientific Reports (2025). DOI: 10.1038/s41598-025-22062-7

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