Understanding the self-ordering of amino acids into supramolecular architectures: co-assembly-based modulation of phenylalanine nanofibrils

Abstract

Amino acids have emerged as promising molecular frameworks for the generation of functional materials owing to the bio-compatibility and thermodynamic stability of their self-assembled architectures. The homogeneous and heterogeneous self-assembly of all naturally occurring amino acids may demonstrate vast functional diversity owing to their common zwitterionic motif, which can serve as a library for the generation of nano/microscale supramolecular biomaterials. Furthermore, amino acids-based self-assembled amyloid structures exhibit pathological relevance, which shifts the paradigm from the self-assembly of polymeric entities to the self-assembly of simple organic molecules or metabolites. Thus, in order to understand the in-built self-ordering behaviour of amino acids, we investigated all naturally occurring amino acids (except aromatic amino acids) for their well-defined morphology and solution-phase β-sheet-like amyloid characteristics. Furthermore, this comprehensive analysis of self-assembly data led to the discovery of aliphatic chain amino acids (ACAAs; Ala, Leu, Ile and Val) as potential candidates for the modulation of phenylalanine fibril toxicity. Thus, this inclusive amino acid self-assembly analysis may pave the way for the design and development of simple organic molecules with inherited self-assembling properties for the generation of functional nanomaterials.