PH-controlled aggregation polymorphism of amyloidogenic Aβ (16-22): Insights for obtaining peptide tapes and peptide nanotubes, as function of the N -terminal capping moiety

Abstract

Peptide and protein self-assembly resulting in the formation of amyloidogenic aggregates is generally thought of as a pathological event associated with severe diseases. However, amyloid formation may also provide a basis for advanced bionanomaterials, since amyloid fibrils combine unique material-like properties that make them very useful for design of new types of conducting nanowires, bioactive ligands, and biodegradable coatings as drug-encapsulating materials. The morphology of the supramolecular aggregates determines the properties and application range of these bionanomaterials. An important parameter to control the supramolecular morphology, is the overall charge of the peptide, which is related to the pH of the environment. Herein, we describe the design, synthesis and morphological analysis of a series of N-terminally functionalized Aβ(16-22) peptides (∼1/4Lys-Leu-Val-Phe-Phe-Ala-Glu-OH), that underwent a pH-induced polymorphism, ranging from lamellar sheets, helical tapes, peptide nanotubes, and amyloid fibrils as was observed by transmission electron microscopy. Infrared spectroscopy and wide angle X-ray scattering studies showed that peptide self-assembly was driven by β-sheet formation, and that the supramolecular morphology was directed by subtle variations in electrostatic interactions. Finally, a structural model and hierarchy of self-assembly of a peptide nanotube, assembled at pH 1, is proposed.