LAUSR

Abstract The diversity of naturally occurring amino acids endows even a very short peptide with an incredible range of sequences, nanostructures and properties. Short peptide sequences have been widely exploited in molecular self-assembly, and this area of research has not only led to a wide range of ordered structures and nanomaterials but also provided insights into protein folding. Conversely, the general physical principles of protein folding accumulated over the past 55 years can be applied to the design of peptide self-assembly. De novo designed surfactant-like peptides (SLPs) are structurally akin to conventional surfactants, with several consecutive hydrophobic amino acids composing their hydrophobic tail region and one or two charged residues making up the hydrophilic head group. Due to their short length, well-defined hydrophobic and hydrophilic regions, innate molecular amphiphilicity, and excellent water solubility, their self-assembly and applications can be orchestrated through molecular design and varying solution conditions. With the canonical 20 amino acids as a starting point, this review introduces the physical principles dictating peptide self-assembly. Then, the major design rules for SLPs, including amino acid substitution, sequence variation, peptide length, amino acid chirality, and incorporation of specific amino acids or sequences, are described, followed by recent advances in their applications for cell culture, antibacterial and anticancer treatments, drug delivery and controlled release, biomimetic mineralization and nanofabrication, hemostasis, and membrane protein stabilization. Finally, a brief outlook to future challenges and opportunities is provided. We hope this review provides a panoramic sketch of SLPs and will inspire more effort into their fundamental research and exploitation.