Design of Modular Peptide Surfactants and Their Surface Activity

Designed peptide surfactants offer a number of advanced properties over conventional petrochemical surfactants, including biocompatibility, sustainability, and tailorability of the chemical and physical properties through peptide design. Their biocompatibility and degradability make them attractive for various applications, particularly for food and pharmaceutical applications. In this work, two new peptide surfactants derived from an amphiphilic peptide surfactant (AM1) were designed (AM-S and C₈-AM) to better understand links between structure, interfacial activity, and emulsification. Based on AM1, which has an interfacial α-helical structure, AM-S and C₈-AM were designed to have two modules, that is, the α-helical AM1 module and an additional hydrophobic moiety to provide for better anchoring at the oil-water interface. Both AM-S and C₈-AM at low bulk concentration of 20 μM were able to adsorb rapidly at the oil-water interface and reduced interfacial tension to equilibrium values of 17.0 and 8.4 mN/m within 400 s, respectively. Their relatively quick adsorption kinetics allowed the formation of nanoemulsions with smaller droplet sizes and narrower size distribution. AM-S and C₈-AM at 800 μM bulk concentration could make nanoemulsions of average diameters 180 and 147 nm, respectively, by simple sonication. With respect to the long-term stability, a minimum peptide concentration of 400 μM for AM-S and a lower concentration of 100 μM for C₈-AM were demonstrated to effectively stabilize nanoemulsions over 3 weeks. Compared to AM1, the AM-S nanoemulsion retained its stimuli-responsive function triggered by metal ions, whereas the C₈-AM nanoemulsions did not respond to the stimuli as efficiently as AM-S because of the strong anchoring ability of the hydrophobic C8 module. The two-module design of AM-S and C₈-AM represents a new strategy in tuning the surface activity of peptide surfactants, offering useful information and guidance of future designs.