Ordered Packing of β-Sheet Nanofibrils into Nanotubes: Multi-hierarchical Assembly of Designed Short Peptides.

Abstract

Although it is well-known proteins and their complexes are hierarchically organized and highly ordered structures, it remains a major challenge to replicate their hierarchical self-assembly process and to fabricate multihierarchical architectures with well-defined shapes and monodisperse characteristic sizes via peptide self-assembly. Here we describe an amphiphilic short peptide Ac-I₃GGHK-NH₂ that first preassembles into thin, left-handed β-sheet nanofibrils, followed by their ordered packing into right-handed nanotubes. The key intermediate morphology and structures featuring the hierarchical process are simultaneously demonstrated. Further mechanistic exploration with the variants Ac-I₃GGGK-NH₂, Ac-I₃GGFK-NH₂, and Ac-I₃GG^<i>D</i>H^<i>D</i>K-NH₂ reveals the vital role of multiple His-His side chain interactions between nanofibrils in mediating higher-order assembly and architectures. Altogether, our findings not only advance current understanding of hierarchical assembly of peptides and proteins but also afford a paradigm of how to take advantage of side chain interactions to construct higher-order assemblies with enhanced complexities.