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<p>Amyloid fibrils, crystal-like fibrillar aggregates of denatured proteins, are formed as a result of the breakdown of supersaturation, causing a series of amyloidosis including Alzheimer’s and Parkinson’s 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., α-synuclein, amyloid β 1–40, and β2-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 β 1–40 were stickier than others, self-associating, adsorbing to loop surfaces, and surging upon flicking the loop, implying early stages of cerebral amyloid angiopathy. On the other hand, β2-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.</p>

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Peristaltic pump-triggered amyloid formation suggests shear stresses are in vivo risks for amyloid nucleation

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年1月31日

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  • Yuji Goto,
  • Tomoki Ota,
  • Wenlou Yuan,
  • Ikuko Yumen,
  • Keiichi Yamaguchi,
  • Hirokazu Matsuda,
  • Suguru Yamamoto,
  • Hirotsugu Ogi

摘要

Amyloid fibrils, crystal-like fibrillar aggregates of denatured proteins, are formed as a result of the breakdown of supersaturation, causing a series of amyloidosis including Alzheimer’s and Parkinson’s 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., α-synuclein, amyloid β 1–40, and β2-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 β 1–40 were stickier than others, self-associating, adsorbing to loop surfaces, and surging upon flicking the loop, implying early stages of cerebral amyloid angiopathy. On the other hand, β2-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.