Bicontinuous microemulsions as a biomembrane mimetic system for melittin

摘要

Abstract Antimicrobial peptides effectively kill antibiotic-resistant bacteria by forming pores in prokaryotes' biomembranes via penetration into the biomembranes' interior. Bicontinuous microemulsions, consisting of interdispersed oil and water nanodomains separated by flexible surfactant monolayers, are potentially valuable for hosting membrane-associated peptides and proteins due to their thermodynamic stability, optical transparency, low viscosity, and high interfacial area. Here, we show that bicontinuous microemulsions formed by negatively-charged surfactants are a robust biomembrane mimetic system for the antimicrobial peptide melittin. When encapsulated in bicontinuous microemulsions formed using three-phase (Winsor-III) systems, melittin's helicity increases greatly due to penetration into the surfactant monolayers, mimicking its behavior in biomembranes. But, the threshold melittin concentration required to achieve these trends is lower for the microemulsions. The extent of penetration was decreased when the interfacial fluidity of the microemulsions was increased. These results suggest the utility of bicontinuous microemulsions for isolation, purification, delivery, and host systems for antimicrobial peptides. Graphical abstract Display Omitted Highlights ? Melittin partitioned to the bicontinuous microemulsion phase of Winsor-III systems. ? The partitioning was driven by electrostatic attractions from anionic surfactants. ? Melittin underwent an increase of α-helicity when solubilized in microemulsions. ? Melittin promoted thinning of the surfactant monolayers, according to SANS. ? Melittin's localized in the surfactant tail region when at low concentrations.