Bicontinuous microemulsions as a biomembrane mimetic system for melittin

Douglas G. Hayes, Ran Ye, Rachel N. Dunlap, Divina B. Anunciado, Sai Venkatesh Pingali, Hugh M. O'Neill, Volker S. Urban

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

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.

Original languageEnglish
Pages (from-to)624-632
Number of pages9
JournalBiochimica et Biophysica Acta - Biomembranes
Volume1860
Issue number2
DOIs
StatePublished - Feb 2018

Funding

This research was supported by the Laboratory Directed Research and Development program of Oak Ridge National Laboratory (ORNL), (grant 6552) . The ORNL Center for Structural Molecular Biology (F.W.P. ERKP291) operates the CG-3 Bio-SANS instrument and is supported by the Office of Biological and Environmental Research of the U.S. Department of Energy (DOE). Research at the High Flux Isotope Reactor of ORNL was sponsored by the Scientific User Facilities Division, Office of Basic Energy Sciences, DOE . Ms. Galina Melnichenko (Water Quality Laboratory, Biosystems Engineering and Soil Science Dept., UT) assisted with the collection of GC–MS data for the quantification of pentanol. Galbraith Laboratories (Knoxville, TN, USA) performed the elemental analysis to determine the concentration of SDS.

Keywords

  • Aerosol-OT
  • Antimicrobial peptides
  • Bicontinuous microemulsions
  • Biomembrane mimetic systems
  • Melittin
  • Small-angle neutron scattering
  • Winsor-III microemulsion systems

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