Peptide-Stabilized Emulsions and Gels from an Arginine-Rich Surfactant-like Peptide with Antimicrobial Activity

Abstract

The preparation of hydrogels and stable emulsions is important in the formulation of many functional nanostructured soft materials. We investigate the multifunctional self-assembly and bioactivity properties of a novel surfactant-like peptide (SLP) that shows antimicrobial activity, is able to form hydrogels without pH adjustment, and is able to stabilize oil-in-water emulsions. Furthermore, we demonstrate on-demand de-emulsification in response to the protease enzyme elastase. We show that SLP (Ala)9-Arg (A9R) forms β-sheet fibers above a critical aggregation concentration and that water-in-oil emulsions are stabilized by a coating of β-sheet fibers around the emulsion droplets. Furthermore, we demonstrate enzyme-responsive de-emulsification, which has potential in the development of responsive release systems. The peptide shows selective antimicrobial activity against Gram-negative pathogens including Pseudomonas aeruginosa, which causes serious infections. Our results highlight the utility of SLPs in the stabilization of oil/water emulsions and the potential for these to be used to formulate antimicrobial peptide emulsions which are additionally responsive to protease. The peptide A9R has pronounced antibacterial activity against clinically challenging pathogens, and its ability to form β-sheet fibers plays a key role in its diverse structural properties, ranging from hydrogel formation to emulsion stabilization.

Peptide nanotubes self-assembled from leucine-rich alpha helical surfactant-like peptides

“…27 We have recently reported on the self-assembly of a number of SLPs with hydrophobic alanine repeats and various charged 'headgroups'. These form b-sheet nanofibrils, 28,29 and in some cases nanotubes. 19,20,30 Here, we explore the self-assembly of SLPs containing leucine repeats instead of alanine sequences, since leucine has a strong a-helix propensity.…”

Amphipathic design dictates self-assembly, cytotoxicity and cell uptake of arginine-rich surfactant-like peptides

“…A major motivation of our study is that amphipathic design has not yet been addressed in the context of isomeric sequences, and arginine-based SLPs such as those described here are a relevant topic due to prominent role of this amino acid in bioactive compounds including cell penetrating 16,17 and antimicrobial peptides. 18,19 Our results show profound effects of amphipathic design on the morphology of self-assembled aggregates and a rich polymorphism emerges with the formation of globular micelles and vesicles, or flat nanotapes and cylindrical micelles, depending on amphiphilic layout and peptide concentration. While the bolaamphiphile variant has been found to show poorer cellpenetrating capabilities, the diblock F4R4 presented good cell uptake rates, being able to reach nucleoli structures and efficiently promote cell death.…”

Self-Assembly, Antimicrobial Activity, and Membrane Interactions of Arginine-Capped Peptide Bola-Amphiphiles

“…CD spectra were recorded as described previously. 8 Samples containing 1 wt % RA 6 R or RA 9 R in pure H 2 O were pipetted into 0.01 mm path length quartz plaque cells or 0.1 mm quartz cuvettes.…”