Peptide amphiphiles (PAs) are peptide-based molecules that self-assemble into supramolecular nanostructures including; spherical micelles, twisted ribbons, and high-aspect-ratio nanofibers.
[5][6] These first reported PA molecules were composed of two domains: one of lipophilic character and another of hydrophilic properties, which allowed self-assembly into sphere-like supramolecular structures as a result of the association of the lipophilic domains away from the solvent (hydrophobic effect), which resulted in the core of the nanostructure.
Work in the laboratory of Samuel I. Stupp by Hartgerink et al., in the early 2000s, reported a new type of PA that are able to self-assemble into elongated nanostructures.
[9][10] The self-assembly mechanism of these PAs is a combination of hydrogen-bonding between beta-sheet forming amino acids and hydrophobic collapse of the tails to yield the formation of cylindrical micelles that present the peptide epitope at extremely high density at the nanofiber surface.
The final structural feature allows the peptide to interact with biomolecules, cells, or proteins, and this is often through epitopes (part of antigens recognised by the immune system).
When aggregation occurs, a variety of assemblies can be formed depending on many parameters such as concentration, pH, temperature and geometry.
[13] Micelles consist of a hydrophobic inner core surrounded by a hydrophilic outer shell that is exposed to a solvent, and their structures can be spheres, disks or wormlike assemblies.
The level of amphiphilicity can vary significantly in peptides and proteins; as such they can display regions that are either hydrophobic or hydrophilic in nature.
Peptide amphiphiles are very useful in biomedical applications, and can be utilised to act as therapeutic agents to treat diseases by transporting drugs across membranes to specific sites.
[20] The modular nature of the chemistry allows the tuning of both the mechanical properties and bioactivities of the resulting self-assembled fibers and gels.
Bioactive sequences can be used to bind growth factors to localize and present them at high densities to cells, or to directly mimic the function of endogenous biomolecules.