This article has been reviewed according to Science X's editorial process and policies. Editors have highlighted the following attributes while ensuring the content's credibility: 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." Doctoral 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." 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.
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