Peristaltic pump flow induces amyloid formation

Researchers from Osaka University found that peristaltic pump flow mechanically breaks supersaturation to induce amyloid formation by hen egg white lysozyme, α-synuclein, amyloid β 1-40, and β2-microglobulin. The high shear stresses induced by peristaltic flow likely reflect those that occur the blood and cerebrospinal fluid, suggesting that this factor could promote amyloidosis.

Overview of peristaltic pump-dependent amyloid inducer with the looped flow of amyloidogenic proteins.

 

Researchers from Osaka University find that peristaltic pump action and high shear flow forces promote amyloid nucleation

Osaka, Japan – The factor that tips you over the edge from being at risk for a disease to actually developing the disease is not always clear. Now, researchers from Japan report one factor that triggers problematic proteins to start behaving badly.

In a study published recently in npj biosensing, researchers from Osaka University have revealed that high liquid flow rates could cause aggregation-prone proteins to start sticking together.

Amyloidosis is the basis of several serious diseases, such as Alzheimer disease and Parkinson disease. This process involves the formation of amyloid fibrils, crystal-like collections of misfolded proteins that clump together when the proteins are highly concentrated (supersaturated) in liquids like blood or cerebrospinal fluid.

Peristaltic pump-dependent amyloid formation of αSN and Aβ40. (a-c) αSN. (d-f) Aβ40. Typical profiles of amyloid formation observed at 485 nm (a, d), fluorescence microscopy images (b, e), and TEM images (c, f) are shown.

“Amyloidosis is a serious concern in our aging society, as elderly individuals are more likely to develop these conditions,” says lead author of the study Yuji Goto. “Although studies have shown that supersaturation is a necessary condition for amyloid fibril formation, the factors that actually induce protein aggregation in supersaturated fluids remain unclear.”

To address this, the researchers ran a model amyloid-forming protein, hen egg white lysozyme, through a peristaltic pump similar to those used for dialysis. They then used fluorescence detection to monitor hen egg white lysozyme amyloid formation as it was propelled through the pump system.

“The results were highly intriguing,” explains Hirotsugu Ogi, senior author. “Flow through the peristaltic pump system effectively triggered amyloid formation by hen egg white lysozyme.”

Next, the researchers tested amyloid-forming proteins associated with human disease, including α-synuclein, amyloid β 1-40, and β2-microglobulin, and found that they also formed amyloids in the peristaltic pump system. Their calculations showed that the shear stress on the liquid caused by the pumping motion mechanically broke supersaturation to induce amyloid formation.

Numerical analysis of shear stress induced in liquid by movement of a contacting rotor. (a) An enlarged view near the rotor located most downstream. (b) Dependence of the maximum shear stress on the number of rotors.

“Our findings suggest that shear flow forces in various fluids in our body, such as blood and cerebrospinal fluid, could trigger amyloid formation,” says Goto.

Given that some medical procedures like dialysis use peristaltic pumps, it is possible that this could be another trigger of amyloidosis. Understanding the effects of shear forces on protein supersaturation could clarify how amyloid aggregates begin to form nucleation and help develop treatment strategies.

Movie:  supersaturation.sakura.ne.jp/PeristalicPump3Feb/Goto_PressRelease_Movie.mp4

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The article, “Peristaltic pump-triggered amyloid formation suggests shear stresses are in vivo risks for amyloid nucleation,” was published in npj biosensing at DOI: https://doi.org/10.1038/s44328-025-00027-0.

About Osaka University
Osaka University 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, Osaka University 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

Published: 18 Feb 2025

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Japan Society for the Promotion of Science