Jump to main content
Jump to site search

Issue 24, 2017
Previous Article Next Article

Model membrane size-dependent amyloidogenesis of Alzheimer's amyloid-β peptides

Author affiliations

Abstract

We herein report the mechanism of amyloid formation of amyloid-β (Aβ) peptides on small (SUV) and large unilamellar vesicles (LUVs), which consist of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) lipids. Although Aβ1–42 formed fibrils on SUVs at all POPC concentrations used, the lag time, elongation rate, maximum thioflavin T intensity, and fibrillar morphology were distinct, indicating polymorphic amyloid formation. LUVs, at low POPC concentrations, did not markedly affect fibrillation kinetics; however, increases in POPC concentrations suppressed amyloid formation. No significant differences in the thermal stabilities of Aβ1–42 fibrils formed with and without vesicles were observed, although fibrils formed on SUVs showed some differences with dilution. SUVs markedly promoted Aβ1–40 fibrillation by condensing Aβ1–40, whereas no effects of LUVs on amyloidogenesis were detected. Salts greatly increased Aβ1–40 amyloidogenicity on vesicles. We proposed comprehensive models for vesicle size-dependent Aβ amyloidogenesis. Inhomogeneous packing defects in SUVs may induce distinct nucleation in the polymorphisms of amyloids and decreasing local concentrations of Aβ with higher amounts of LUVs inhibits amyloid formation. We also pointed out that C-terminal hydrophobicity of Aβ is important for amyloidogenesis on membranes.

Graphical abstract: Model membrane size-dependent amyloidogenesis of Alzheimer's amyloid-β peptides

Back to tab navigation

Supplementary files

Publication details

The article was received on 14 Nov 2016, accepted on 25 May 2017 and first published on 26 May 2017


Article type: Paper
DOI: 10.1039/C6CP07774A
Citation: Phys. Chem. Chem. Phys., 2017,19, 16257-16266
  •   Request permissions

    Model membrane size-dependent amyloidogenesis of Alzheimer's amyloid-β peptides

    M. Kinoshita, E. Kakimoto, M. S. Terakawa, Y. Lin, T. Ikenoue, M. So, T. Sugiki, A. Ramamoorthy, Y. Goto and Y. Lee, Phys. Chem. Chem. Phys., 2017, 19, 16257
    DOI: 10.1039/C6CP07774A

Search articles by author

Spotlight

Advertisements