The self-assembly of short aromatic peptides and peptide derivatives into a variety of different nano- and microstructures (fibrillar gels, crystals, spheres, plates) is a promising route toward the creation of bio-compatible materials with often unexpected and useful properties. Furthermore, such simple self-assembling systems have been proposed as model systems for the self-assembly of longer peptides, a process that can be linked to biological function and malfunction. Much effort has been made in the last 15 years to explore the space of peptide sequences, chemical modifications and solvent conditions in order to maximise the diversity of assembly morphologies and properties. However, quantitative studies of the corresponding mechanisms of, and driving forces for, peptide self-assembly have remained relatively scarce until recently. In this chapter we review the current state of understanding of the thermodynamic driving forces and self-assembly mechanisms of short aromatic peptides into supramolecular structures. We will focus on experimental studies of the assembly process and our perspective will be centered around diphenylalanine (FF), a key motif of the amyloid β sequence and a paradigmatic self-assembly building block. Our main focus is the basic physical chemistry and key structural aspects of such systems, and we will also compare the mechanism of dipeptide aggregation with that of longer peptide sequences into amyloid fibrils, with discussion on how these mechanisms may be revealed through detailed analysis of growth kinetics, thermodynamics and other fundamental properties of the aggregation process.
Keywords: Amyloid; Aromaticity; Biomaterials; Crystal; FF; Fibril; Gel; Microfluidics; Nucleation; Self-assembly.