Impact of membrane curvature on amyloid aggregation

Mayu S. Terakawa, Yuxi Lin, Misaki Kinoshita, Shingo Kanemura, Dai Itoh, Toshihiko Sugiki, Masaki Okumura, Ayyalusamy Ramamoorthy, Young Ho Lee

Research output: Contribution to journalReview articlepeer-review

74 Citations (Scopus)


The misfolding, amyloid aggregation, and fibril formation of intrinsically disordered proteins/peptides (or amyloid proteins) have been shown to cause a number of disorders. The underlying mechanisms of amyloid fibrillation and structural properties of amyloidogenic precursors, intermediates, and amyloid fibrils have been elucidated in detail; however, in-depth examinations on physiologically relevant contributing factors that induce amyloidogenesis and lead to cell death remain challenging. A large number of studies have attempted to characterize the roles of biomembranes on protein aggregation and membrane-mediated cell death by designing various membrane components, such as gangliosides, cholesterol, and other lipid compositions, and by using various membrane mimetics, including liposomes, bicelles, and different types of lipid-nanodiscs. We herein review the dynamic effects of membrane curvature on amyloid generation and the inhibition of amyloidogenic proteins and peptides, and also discuss how amyloid formation affects membrane curvature and integrity, which are key for understanding relationships with cell death. Small unilamellar vesicles with high curvature and large unilamellar vesicles with low curvature have been demonstrated to exhibit different capabilities to induce the nucleation, amyloid formation, and inhibition of amyloid-β peptides and α-synuclein. Polymorphic amyloidogenesis in small unilamellar vesicles was revealed and may be viewed as one of the generic properties of interprotein interaction-dominated amyloid formation. Several mechanical models and phase diagrams are comprehensively shown to better explain experimental findings. The negative membrane curvature-mediated mechanisms responsible for the toxicity of pancreatic β cells by the amyloid aggregation of human islet amyloid polypeptide (IAPP) and binding of the precursors of the semen-derived enhancer of viral infection (SEVI) are also described. The curvature-dependent binding modes of several types of islet amyloid polypeptides with high-resolution NMR structures are also discussed.

Original languageEnglish
Pages (from-to)1741-1764
Number of pages24
JournalBiochimica et Biophysica Acta - Biomembranes
Issue number9
Publication statusPublished - 2018 Sept


  • Alpha-synuclein
  • Amyloid-beta
  • hIAPP
  • HIV
  • Membrane interaction
  • Protein misfolding disease
  • SEVI


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