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

Abstract

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

Authors:
 [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:
Research Org.:
Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States). Spallation Neutron Source (SNS); Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States). Center for Structural Molecular Biology (CSMB)
Sponsoring Org.:
USDOE Laboratory Directed Research and Development (LDRD) Program; USDOE Office of Science (SC), Biological and Environmental Research (BER) (SC-23); USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22)
OSTI Identifier:
1406384
Grant/Contract Number:
AC05-00OR22725; FWP ERKP291; LDRD-6436
Resource Type:
Journal Article: Published Article
Journal Name:
Biochimica et Biophysica Acta. Biomembranes
Additional Journal Information:
Journal Volume: 1858; Journal Issue: 11; Journal ID: ISSN 0005-2736
Publisher:
Elsevier
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; membrane-active peptide; melittin; small-angle neutron scattering; phosphatidylserine; membrane asymmetry

Citation Formats

Rai, Durgesh K., Qian, Shuo, and Heller, William T. The Interaction of Melittin with Dimyristoyl Phosphatidylcholine-Dimyristoyl Phosphatidylserine Lipid Bilayer Membranes. United States: N. p., 2016. Web. doi:10.1016/j.bbamem.2016.08.006.
Rai, Durgesh K., Qian, Shuo, & Heller, William T. The Interaction of Melittin with Dimyristoyl Phosphatidylcholine-Dimyristoyl Phosphatidylserine Lipid Bilayer Membranes. United States. doi:10.1016/j.bbamem.2016.08.006.
Rai, Durgesh K., Qian, Shuo, and Heller, William T. 2016. "The Interaction of Melittin with Dimyristoyl Phosphatidylcholine-Dimyristoyl Phosphatidylserine Lipid Bilayer Membranes". United States. doi:10.1016/j.bbamem.2016.08.006.
@article{osti_1406384,
title = {The Interaction of Melittin with Dimyristoyl Phosphatidylcholine-Dimyristoyl Phosphatidylserine Lipid Bilayer Membranes},
author = {Rai, Durgesh K. and Qian, Shuo and Heller, William T.},
abstractNote = {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 headgroup region of the lipid bilayer. Lastly, the results provide new information about lipid-specific interactions that take place in mixed composition lipid bilayer membranes.},
doi = {10.1016/j.bbamem.2016.08.006},
journal = {Biochimica et Biophysica Acta. Biomembranes},
number = 11,
volume = 1858,
place = {United States},
year = 2016,
month = 8
}

Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record at 10.1016/j.bbamem.2016.08.006

Citation Metrics:
Cited by: 1work
Citation information provided by
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  • 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 andmore » 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 headgroup 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
  • The binding of melittin to nonsonicated bilayer membranes composed of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine was studied with an ultracentrifugation assay and with {sup 2}H and {sup 31}P nuclear magnetic resonance. Melittin binding could best be described by a partition equilibrium with K{sub p} = (2.1 {plus minus} 0.2) {times} 10{sup 3} M{sup {minus}1}, measuring the binding isotherm in the concentration range of 0-100 {mu}M melittin and taking into account electrostatic effects by means of the Gouy-Chapman theory. This partition coefficient is smaller than that deduced for small sonicated vesicles and attests to the tighter lipid packing in the nonsonicated bilayers. Deuterium magnetic resonancemore » revealed a conformational change of the phosphocholine head group upon melittin binding. The quadrupole splittings of the {alpha} and {beta} segments of the choline head group varied linearly with the amount of bound melittin but in opposite directions; i.e., the {alpha} splitting decreased, and the {beta} splitting increased. This conformational change is not specific to melittin but is a response of the phosphocholine head group to positive membrane surface charges in general. Quantitatively, melittin is one of the most efficient head-group modulators, the efficiency per unit charge comparable to that of charged local anesthetics or hydrophobic ions.« less
  • The peptide melittin, a 26 amino acid, cationic peptide from honey bee ( Apis mellifera) venom, disrupts lipid bilayer membranes in a concentration-dependent manner. Rather than interacting with a specific receptor, the peptide interacts directly with the lipid matrix of the membrane in a manner dependent on the lipid composition. Here, a small-angle neutron scattering study of the interaction of melittin with lipid bilayers made of mixtures of dimyristoylphosphatidylcholine (DMPC) and cholesterol (Chol) is presented. Through the use of deuterium-labeled DMPC, changes in the distribution of the lipid and cholesterol in unilamellar vesicles were observed for peptide concentrations below thosemore » that cause pores to form. In addition to disrupting the in-plane organization of Chol, melittin produces vesicles having inner and outer leaflet compositions that depend on the lipid–Chol molar ratio and on the peptide concentration. The changes seen at high cholesterol and low peptide concentration are similar to those produced by alamethicin (Qian, S. et al., J. Phys. Chem. B 2014, 118, 11200–11208), which points to an underlying physical mechanism driving the redistribution of Chol, but melittin displays an additional effect not seen with alamethicin. Furthermore, a model for how the peptide drives the redistribution of Chol is proposed. The results suggest that redistribution of the lipids in a target cell membrane by membrane active peptides takes places as a prelude to the lysis of the cell.« less