Researchers from the University of Osaka find that a protein associated with amyloidogenic light chain disease preferentially forms amyloid in areas of constrained geometry when subjected to shear stress, such as in coronary arterioles
Osaka, Japan – Many cars and not enough lanes is a recipe for traffic jams. Now, researchers from Japan show that even proteins can get backed up and start behaving poorly when too many try to squeeze too quickly through a small space.
In a study that has been published in
FEBS Journal, researchers from the University of Osaka have reported real-time observation of the formation of amyloid (a crystal-like protein aggregate) triggered by shear stress.
Amyloid fibrils occur in diseases like Alzheimer’s and Parkinson’s. In amyloidogenic light chain disease, these fibrils accumulate in the heart, where they are subjected to shear stress due to blood flow and changing blood vessel sizes caused by the heart beating.
“The shear stress exerted on proteins within cardiac blood vessels is thought to promote amyloid formation,” says lead author of the study Yuji Goto. “However, the mechanism underlying this effect remains unclear, as it is difficult to design an artificial model that mimics the changes in volume and mechanical stress induced by cardiac function.”
To address this, the researchers used a peristaltic pump, which alternately compresses and releases the pressure on a flexible tube to move fluid through in waves. Using thioflavin T fluorescence microscopy (a method that detects aggregated proteins), they tracked the formation of amyloid by a protein associated with heart amyloidosis within the tube.
“The results were very intriguing,” states Hirotsugu Ogi, senior author. “We saw that fibrils started to form in the narrow vertices of the semicircular tubing, suggesting that spatial constraint enhanced amyloid formation in the presence of shear stress.”
When the protein solution was pumped through a microchannel grid, amyloids tended to form at the intersections of perpendicular channels and could be partly cleared by pushing down on a nearby channel to change the pressure of the flow. Adding guanidine hydrochloride, which helps unfold and dissolve proteins, completely cleared the remaining amyloids from the grid system. In a separate experiment using the peristaltic pump setup, the team found that green tea compound epigallocatechin gallate could both prevent and reverse amyloid formation in two different ways depending on the concentration used, one of which had not been seen before.
“Our results show that amyloid formation and deposition in blood vessels occur due in part to both mechanical stress and blood vessel geometry,” says Goto.
By combining a peristaltic pump and microchannels with fluorescence microscopy, the research team achieved the difficult feat of observing the early stages of amyloid formation. Their findings suggest that a combination of mechanical pressure and chemical inhibitors could help dissolve amyloids after they have formed. More broadly, pinpointing these triggers may help researchers better understand how amyloidosis develops and support future efforts to assess disease risk.
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The article, “Constrictions and shear stress are key determinants of amyloidogenic light chain (AL) amyloidosis,” was published in
FEBS Journal at DOI: https://doi.org/10.1111/febs.70691
Movie
Caption: Peristaltic pump-dependent amyloid formation with a grid-type microchannel.
License：Original content
Usage restriction: No restrictions
Credit: Yuji Goto
Adapted from Movie S6 of "Constrictions and shear stress are key determinants of amyloidogenic light chain (AL) amyloidosis" by Yuji Goto et al., 2026,
FEBS Journal.
About The University of Osaka
The University of Osaka was founded in 1931 as one of the seven imperial universities of Japan and is now one of Japan's leading comprehensive universities with a broad disciplinary spectrum. This strength is coupled with a singular drive for innovation that extends throughout the scientific process, from fundamental research to the creation of applied technology with positive economic impacts. Its commitment to innovation has been recognized in Japan and around the world. Now, The University of Osaka is leveraging its role as a Designated National University Corporation selected by the Ministry of Education, Culture, Sports, Science and Technology to contribute to innovation for human welfare, sustainable development of society, and social transformation.
Website:
https://resou.osaka-u.ac.jp/en