Air/water Interface Induced Folding And Self-assembly Of Amyloid-beta Peptide

Abstract

The amphipacity of the natively unstructured amyloid-beta (Ab40) peptide may play an important role in its aggregation into beta-sheet rich fibrils that is linked to the pathogenesis of Alzheimer's disease. Using the air/water interface as an ideal hydrophobic interface, we characterized Ab's surface activity and the structure, assembly, and morphology of Ab adsorbed to the air/water interface. Ab dissolved in water readily adsorbed to the air/water interface to form a contiguous film with a surface pressure of approximately 14 mN/m and showed an apparent critical micelle concentration of about 100 nM. Adsorbed Ab was composed of a single molecular layer extending approximately 20 A into the aqueous subphase with in-plane ordering that gave rise to X-ray diffraction peaks. Analysis of the diffraction peaks showed that the air/water interface induced the otherwise unstructured Ab peptides to self-assemble into nano-size clusters with Ab peptides folded in a beta-sheet conformation. The presence of these clusters was further confirmed by imaging the morphology of the Ab film using atomic force microscopy. The formation of these ordered clusters was not affected by solution pH, ionic strength, or the presence of cosolutes sucrose and urea at concentrations that are known to stabilize and denature native proteins in solution, suggesting that the hydrophobic interface-driven Ab folding and assembly is robust and strongly favorable. Furthermore, Ab adsorbed at the air/water interface can seed fibril growth in solution when re-introduced into the bulk. Our results implicate that that interface-induced Ab folding and self-assembly may serve as a mechanism by which Ab aggregation occurs in vivo.