skip to main content


Title: The Interaction of Melittin with Dimyristoyl Phosphatidylcholine-Dimyristoyl Phosphatidylserine Lipid Bilayer Membranes

We report that membrane-active peptides (MAPs), which interact directly with the lipid bilayer of a cell and include toxins and host defense peptides, display lipid composition-dependent activity. Phosphatidylserine (PS) lipids are anionic lipids that are found throughout the cellular membranes of most eukaryotic organisms where they serve as both a functional component and as a precursor to phosphatidylethanolamine lipids. The inner leaflet of the plasma membrane contains more PS than the outer one, and the asymmetry is actively maintained. Here, the impact of the MAP melittin on the structure of lipid bilayer vesicles made of a mixture of phosphatidylcholine and phosphatidylserine was studied. Small-angle neutron scattering of the MAP associated with selectively deuterium-labeled lipid bilayer vesicles revealed how the thickness and lipid composition of phosphatidylserine-containing vesicles change in response to melittin. The peptide thickens the lipid bilayer for concentrations up to P/L = 1/500, but membrane thinning results when P/L = 1/200. The thickness transition is accompanied by a large change in the distribution of DMPS between the leaflets of the bilayer. The change in composition is driven by electrostatic interactions, while the change in bilayer thickness is driven by changes in the interaction of the peptide with the headgroupmore » region of the lipid bilayer. Lastly, the results provide new information about lipid-specific interactions that take place in mixed composition lipid bilayer membranes.« less
 [1] ;  [2] ;  [1]
  1. Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States). Biology & Soft Matter Division
  2. Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States). Biology & Soft Matter Division; Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States). Center for Structural Molecular Biology
Publication Date:
Grant/Contract Number:
AC05-00OR22725; FWP ERKP291
Accepted Manuscript
Journal Name:
Biochimica et Biophysica Acta. Biomembranes
Additional Journal Information:
Journal Volume: 1858; Journal Issue: 11; Journal ID: ISSN 0005-2736
Research Org:
Oak Ridge National Laboratory (ORNL), Oak Ridge, TN (United States). Spallation Neutron Source; Center for Structural Molecular Biology (CSMB)
Sponsoring Org:
ORNL LDRD Director's R&D;USDOE Office of Science (SC), Biological and Environmental Research (BER) (SC-23)
Country of Publication:
United States
59 BASIC BIOLOGICAL SCIENCES membrane-active peptide; melittin; small-angle neutron scattering; phosphatidylserine; membrane asymmetry
OSTI Identifier:
Alternate Identifier(s):
OSTI ID: 1311221