Self-assembly of peptides: influence of substrate, pH and medium on the formation of supramolecular assemblies

Abstract

Molecular self-assembly is a natural process occurring in many pathological conditions including Alzheimer's disease. Mechanistic insight into the self-assembly of amyloid fibrils led to the discovery of an aromatic dipeptide (diphenylalanine, FF) which is present in the core structural motif of Alzheimer's beta amyloid polypeptide. FF dipeptide has been reported to form well-defined nanotubes, which has been envisaged as a potential beta strand breaker in combination with charged amino acids for treating Alzheimer's disease. For therapeutic applications, it becomes important to consider the influence of hydrophobicity, temperature, pH, salts, proteins and peptide concentration on the self-assembly process which is the main focus of the present work. In the current study, we have qualitatively evaluated the morphological changes of FF nanostructures under various experimental conditions by scanning electron microscopy. Fourier Transform Infra-Red studies confirmed intermolecular hydrogen bonding and presence of parallel beta sheet structures. The scanning electron micrographs show formation of FF nanotubes under various conditions. The dimensions of the self-assembled nanostructures were found to be strongly influenced by the substrate, temperature, pH, salts and proteins. FF nanostructures formed under all experimental conditions showed enhanced fluorescence with Thioflavin T confirming the presence of beta sheet structures. The formation of peptide nanotubes in the physiological experimental conditions makes them attractive tool for future bionanotechnological applications.