Minimal Peptide Surfactants for Long-Lasting Nanoemulsions via Noncovalent Interfacial Interactions.

Peptide-based surfactants offer a biodegradable and highly tunable alternative to conventional amphiphilic stabilizers for pharmaceutical and biotechnological applications. However, their broader industrial translation is often limited by the high production costs and environmental sensitivity of long peptide sequences. Here, we present a modular design strategy based on short heptad repeat motifs to develop minimal-length peptide emulsifiers capable of forming robust interfacial architectures. By leveraging predictable interpeptide interactions driven by hydrophobic residues and electrostatic attraction at the c, e, and f positions, the designed peptides exhibit efficient adsorption at the oil-water interface. The representative peptide, 5F7H, stabilizes nanoemulsions with a monodispersed droplet size of ∼170 nm for more than 15 months, achieving approximately 79% interfacial adsorption. Molecular simulations suggest partial helical organization, supporting the formation of a densely packed yet dynamic interfacial layer. The system demonstrates enhanced surface activity at a basic pH and strong resistance to dilution, indicating robust interfacial cohesion. These findings establish a minimalistic peptide design principle for constructing durable nanoemulsion systems and provide a foundation for scalable, bioderived emulsifiers in advanced formulation technologies.