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bioRxiv · 10.1101/2024.09.16.613380

Peristaltic pump-triggered amyloid formation suggests shear stresses are in vivo risk factors of amyloid nucleation

Goto, Y.·Ota, T.·Yuan, W.·Yumen, I.·Yamaguchi, K.·Matsuda, H.·Yamamoto, S.·Ogi, H.
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Abstract

Amyloid fibrils, crystal-like fibrillar aggregates of denatured proteins, are formed linked with the breakdown of supersaturation, causing a series of amyloidosis including Alzheimers and Parkinsons diseases. Although varying in vitro factors are known, in vivo factors breaking supersaturation are unclear. We found that flowing by a peristaltic pump effectively triggers amyloid formation of hen egg white lysozyme, a model amyloidogenic protein, and, moreover, amyloidosis-associated proteins (i.e. -synuclein, amyloid {beta} 1-40, and {beta}2-microglobulin). The peristaltic pump-dependent amyloid formation was visualized by a fluorescence microscope with looped flow system, revealing dynamic motions under flow. Among them, amyloid fibrils of amyloid {beta} 1-40 were stickier than others, self-associating, absorbing to loop surfaces, and surging upon flicking the loop, implying early stages of cerebral amyloid angiopathy. On the other hand, {beta}2-microglobulin at a neutral pH showed unique two-step amyloid formation with an oligomeric trapped intermediate, which might mimic amyloid formation in patients. Peristalsis-caused strong shear stresses were considered to mechanically break supersaturation. Shearing stresses occur in vivo at varying levels, suggesting that they break otherwise persistent supersaturation, thus triggering amyloid formation and ultimately leading to amyloidosis. (182 words <200 words)

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Goto, Y., Ota, T., Yuan, W., Yumen, I., Yamaguchi, K., Matsuda, H., Yamamoto, S., Ogi, H.. 2024-09-19. Peristaltic pump-triggered amyloid formation suggests shear stresses are in vivo risk factors of amyloid nucleation. https://doi.org/10.1101/2024.09.16.613380

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