Composition effects on the self-aggregation of phenylalanine-rich oligopeptides revealed by atomic force microscopy

Abstract

The emergency of peptide-assembled nanomaterials motivates the efforts towards understanding the composition effects governing the assembly structure of peptides. Herein, we used time-lapse atomic force microscopy (AFM) to characterize the time-dependent structural transformation of phenylalanine (F)-rich self-assembled peptides and elucidated the impacts of composition heterogeneity on modulating peptide aggregation. Four binary peptides (F5Y5, F5A5, F5H5, and F5D5) were synthesized to arrange distinct types of amino acids, including aromatic tyrosine (Y), nonpolar alanine (A), cationic histidine (H), and anionic aspartic acid (D), in the proximity of an F-rich moiety. We compared the time-dependent structural transitions of these peptide assemblies using AFM. F5Y5 and F5A5 were observed to form fibril-like aggregates over time, whereas F5H5 and F5D5 assembled into globular particles during the time course examined. The impacts of neighboring amino acids on affecting F-rich peptide fibrillation are in line with the hydrophobicity scales of amino acid side chains. Specifically, Y and A facilitate the fibril aggregation, whereas H and D hinder the fibril formation of F-rich peptides. Our results manifest the hydrophobicity of amino acids proximal to the F residues is important for the fibril-like aggregation of peptides.

Graphical abstract