Abstract
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 those 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. 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.
| Original language | English |
|---|---|
| Pages (from-to) | 2253-2260 |
| Number of pages | 8 |
| Journal | Biochimica et Biophysica Acta - Biomembranes |
| Volume | 1848 |
| Issue number | 10 |
| DOIs | |
| State | Published - Jul 13 2015 |
Funding
A portion of this work was supported by the Laboratory Directed Research and Development program of Oak Ridge National Laboratory . The Oak Ridge National Laboratory Center for Structural Molecular Biology ( FWP ERKP291 ) is supported by the Office of Biological and Environmental Research of the US Department of Energy . Research at the High Flux Isotope Reactor and at the Spallation Neutron Source of Oak Ridge National Laboratory was sponsored by the Scientific User Facilities Division, Office of Basic Energy Sciences, US Department of Energy . Notice: This manuscript has been authored by UT-Battelle, LLC, under Contract No. DE-AC0500OR22725 with the U.S. Department of Energy. The United States Government retains and the publisher, by accepting the article for publication, acknowledges that the United States Government retains a non-exclusive, paid-up, irrevocable, world-wide license to publish or reproduce the published form of this manuscript, or allow others to do so, for the United States Government purposes. The Department of Energy will provide access to these results of federally sponsored research in accordance with the DOE Public Access Plan ( http://energy.gov/downloads/doe-public-access-plan ).
| Funders | Funder number |
|---|---|
| Oak Ridge National Laboratory | FWP ERKP291 |
| Scientific User Facilities Division | |
| U.S. Department of Energy | |
| Basic Energy Sciences | |
| Biological and Environmental Research | |
| Oak Ridge National Laboratory |
Keywords
- Cholesterol
- Lipid bilayers
- Melittin
- Membrane active peptides
- Small-angle neutron scattering