Controlling Supramolecular Chiral Nanostructures by Self-Assembly of a Biomimetic β-Sheet-Rich Amyloidogenic Peptide

Squid sucker ring teeth (SRT) have emerged as a promising protein-only, thermoplastic biopolymer with an increasing number of biomedical and engineering applications demonstrated in recent years. SRT is a supra-molecular network whereby a flexible, amorphous matrix is mechanically reinforced by nanoconfined β-sheets. The building blocks for the SRT network are a family of suckerin proteins that share a common block copolymer architecture consisting of amorphous domains intervened by smaller, β-sheet forming modules. Recent studies have identified the peptide A1H1 (peptide sequence AATAVSHTTHHA) as one of the most abundant β-sheet forming domains within the suckerin protein family. However, we still have little understanding of the assembly mechanisms by which the A1H1 peptide may assemble into its functional load-bearing domains. In this study, we conduct a detailed self-assembly study of A1H1 and show that the peptide undergoes β-strands-driven elongation into amyloid-like fibrils with a rich polymorphism. The nanostructure of the fibrils was elucidated by small and wide-angle X-ray scattering (SAXS and WAXS) and atomic force microscopy (AFM). The presence of His-rich and Ala-rich segments results in an amphiphilic behavior and drives its assembly into fibrillar supramolecular chiral aggregates with helical ribbon configuration in solution, with the His-rich region exposed to the solvent molecules. Upon increase in concentration, the fibrils undergo gel formation, while preserving the same mesoscopic features. This complex phase behavior suggests that the repeat peptide modules of suckerins may be manipulated beyond their native biological environment to produce a wider variety of self-assembled amyloid-like nanostructures.