As a fundamental property of peptide molecules, chirality has been demonstrated to play an important role in controlling the structures and characteristics of peptide supramolecular systems. However, the mechanism through which chirality takes effect has not been clarified.

This study aims to examine the self- and co-assembled nanostructures and analyze the intermolecular interactions that drive the assembly by employing diphenylalanine (FF), along with the core recognition sequence of Amyloid-β protein (Aβ) and its enantiomer _D-Phe-_D-Phe (ff), in a model system.

A series of structural and morphological analyses were conducted in the experiments. First, the scanning electron microscopy (SEM) and atomic force microscopy (AFM) images of the assembled nanostructures were obtained to observe the microscopic morphology and topological structure of the assembled FF and ff. Subsequently, circular dichroism (CD) and Fourier transform infrared spectroscopy (FTIR) were employed to characterize the secondary structures of peptides in the nanostructures. Finally, fluorescence emission spectrum and X-ray diffraction (XRD) analyses revealed the intermolecular interactions between peptide and solvent molecules.

The findings demonstrate that FF and ff self-assemble into similar fibrous nanostructures, and their chirality primarily affects the interactions between peptide molecules, as well as those between peptide and water molecules. Furthermore, the formation of new crystalline phases for the co-assembly of FF and ff was confirmed by XRD.

Our results may facilitate the understanding of the formation mechanism of amyloid fibers and design of peptide supramolecular materials.