Supersaturation-limited Amyloid fibrillation of Insulin revealed by ultrasonication

Hiroya Muta, Young Ho Lee, József Kardos, Yuxi Lin, Hisashi Yagi, Yuji Goto

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Amyloid fibrils form in supersaturated solutions via a nucleation and growth mechanism.Weproposed that ultrasonication may be an effective agitation to trigger nucleation that would otherwise not occur under the persistent metastability of supersaturation. However, the roles of supersaturation and effects of ultrasonication have not been elucidated in detail except for limited cases. Insulin is an amyloidogenic protein that is useful for investigating the mechanisms underlying amyloid fibrillation with biological relevance. We studied the alcohol-induced amyloid fibrillation of insulin using various concentrations of 2,2,2-trifluoroethanol and 1,1,1,3,3,3-hexafluoro-2-propanol at pH2.0 and 4.8. Ultrasonic irradiation effectively triggered fibrillation under conditions in which insulin retained persistent supersaturation. Structural analyses by circular dichroism, Fourier transform infrared spectroscopy, transmission electron microscopy, and atomic force microscopy revealed that the dominant structures of fibrils varied between parallel and antiparallel β-sheets depending on the solvent conditions. pH and alcohol concentration-dependent phase diagrams showed a marked difference before and after the ultrasonic treatment, which indicated that the persistent metastability of supersaturation determined the conformations of insulin. These results indicate the importance of an alternative view of amyloid fibrils as supersaturation-limited crystal-like aggregates formed above the solubility limit.

Original languageEnglish
Pages (from-to)18228-18238
Number of pages11
JournalJournal of Biological Chemistry
Volume289
Issue number26
DOIs
Publication statusPublished - Jun 27 2014

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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