RESUMO
We herein report the mechanism of amyloid formation of amyloid-ß (Aß) peptides on small (SUV) and large unilamellar vesicles (LUVs), which consist of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) lipids. Although Aß1-42 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 Aß1-42 fibrils formed with and without vesicles were observed, although fibrils formed on SUVs showed some differences with dilution. SUVs markedly promoted Aß1-40 fibrillation by condensing Aß1-40, whereas no effects of LUVs on amyloidogenesis were detected. Salts greatly increased Aß1-40 amyloidogenicity on vesicles. We proposed comprehensive models for vesicle size-dependent Aß amyloidogenesis. Inhomogeneous packing defects in SUVs may induce distinct nucleation in the polymorphisms of amyloids and decreasing local concentrations of Aß with higher amounts of LUVs inhibits amyloid formation. We also pointed out that C-terminal hydrophobicity of Aß is important for amyloidogenesis on membranes.
