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Some proteins that are linked to neurodegenerative diseases can form both liquid droplets and amyloid fibers. But how are these two states connected, and where do the fibers grow? Leiden physicists Liru Feng and Louise Jawerth have discovered a counter-intuitive mechanism.
"We wanted to answer an open question: What happens to protein droplets as they age?" assistant professor Jawerth explains. "They look just like drops of oil in water, but they are droplets of proteins inside cells, also called condensates. Scientists have only relatively recently come to understand how they develop. Our findings on how they age—published in Nature Physics today—add an important piece to the puzzle."
The droplets are very complex materials; they are liquid-like and can turn into solids that are glassy or fibrous. Jawerth states, "For 10 years or so, we have known that there is a link between fiber growth from these proteins and neurodegenerative disorders like Alzheimer's disease or ALS. Our goal was to visualize, quantify and model this aging process, and we succeeded in doing so."
Unveiling the mysteryDoctoral candidate Feng describes how small these protein droplets are: "They are only about 5 micrometers across—around 10 times thinner than the width of a human hair." With a confocal microscope, Feng monitored the samples in 3D for 12 hours. They revealed and quantified the development of the liquid droplets into both possible solid states: glassy and fibrous.
The team did not expect to uncover a whole new paradigm of fiber growth, but they did.
"The results truly surprised us," says Jawerth. "We have often thought that fibers would grow on the inside of the droplets where there is a high concentration of protein, but now we know they don't. They grow from the surface to the outside. Meanwhile, as these fibers grow, we see the droplets themselves shrink and become glasslike."
The aging process of a protein droplet made visible through a 12-hour time-lapse. Credit: Leiden Institute of Physics Two competing ways of aging
In their data analysis, the physicists showed that the fibers and glasslike state are two different solid forms of the same protein. They represent two competing ways in which the protein system can age. This means that they can exist side by side, but one does not directly change into the other. Feng states, "In our experiments, we made this visible by first aging the proteins for two days before initiating fiber growth. You see that this way, the aged droplets hardly grow any fibers."
"This means new theoretical models are needed to understand and predict these processes," concludes Jawerth. Together with theoretical physicists at the Max Planck Institute, the team developed these new theoretical frameworks.
A 12-hour time-lapse of protein droplets, also called condensates. Credit: Leiden Institute of Physics Full-time experimenting
"Key to our success was the fact that our lab has two confocal microscopes that are available full-time for our group. These microscopes use laser light to create detailed images of cells and tissues. A luxury that many other groups don't have," says Jawerth.
"Also, Feng is clearly a very talented experimentalist. It's no simple challenge to make something visible in a microscope that nobody else has seen before. Moreover, you need to take this zoo of observations from the microscope and build a new conceptual framework of the underlying physics. To answer the question: What do all these observations tell us?"
A new view on existing data"With our fundamental research on aging proteins, we've created clarity. I think it immediately will give my fellow researchers—from biologists to doctors—a new view on their data. Cells are extraordinarily complex systems, and if we are also confused—on top of this complexity—about the way simple cell elements like proteins function, then resolving the bigger questions is impossible. Now that we know what's happening in proteins, we are ready to take the next steps."
Healthy or unhealthy aging"We don't yet know the healthy versus unhealthy routes for aging protein droplets," Jawerth concludes. "At this moment in time, our work suggests that the glassy state of aging may have a different, perhaps even healthy, function within brain cells, while the fibers are possibly the unhealthy alternative.
"Mind you, we don't know yet if these fibers are the main reason brain cells degenerate. By clarifying how the fundamental processes work, we can at least more clearly analyze the complex data we get when we look into cells. In our lab, we made an important step toward this goal."
Publication detailsLiru Feng et al., Fibres and glasses are competing material states in protein condensation, Nature Physics (2026). DOI: 10.1038/s41567-026-03415-z. On bioRxiv: www.biorxiv.org/content/10.648 … /2026.09.28.754945v1
Who's behind this story?
Lisa LockBA art history, MA material culture. Former museum editor, paramedic, and transplant coordinator. Editing for Science X since 2021. Full profile →
Robert EganBachelor's in mathematical biology, Master's in creative writing. Well-traveled with unique perspectives on science and language. Full profile →
Citation: Physicists reveal new paradigm for fiber growth in neurodegenerative diseases (2026, October 26) retrieved 26 October 2026 from https://phys.org/news/2026-10-physicists-reveal-paradigm-fiber-growth.html
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