Peptide self-assembly represents a versatile and programmable strategy for generating functional nanomaterials with broad biomedical relevance. This review outlines the physicochemical principles governing assembly, highlighting cooperative noncovalent interactions, hydrogen bonding, π-π stacking, electrostatics and hydrophobic forces that drive hierarchical organisation into supramolecular structures. Key analytical techniques for characterising peptide assemblies and nanostructures are also summarised. The contribution of secondary structural motifs, particularly α-helices and β-sheets, is explored in relation to morphology, stability and biological function. α-Helical coiled-coil peptides form well-defined nanotubular architectures suitable for cargo encapsulation, whereas β-sheet peptides assemble into nanofibrillar networks and hydrogels with tuneable mechanical properties and sustained release profiles, as illustrated by systems such as RQDL10. Beyond peptides, protein and DNA self-assembly further expand the biomolecular design space. Protein-based systems leverage hydrophobic and Debye-Hückel electrostatic interactions to build hierarchical, functional architectures. DNA platforms enable programmable, stimulus-responsive assembly, including enzyme- and logic-controlled activation and hybridisation-driven formation of reversible higher-order nanostructures. Applications in drug delivery, tissue engineering and regenerative medicine are discussed alongside challenges such as limited in vivo stability, proteolytic degradation and scalability. Emerging approaches-including rational design, sequence engineering and advanced fabrication-aim to improve predictability and reproducibility, positioning biomolecular self-assembly as a unified platform for next-generation biomaterials.
Fares et al. (2026) studied this question.