title: Gramicidin A Channel Formation Induces Local Lipid Redistribution I: Experiment and Simulation.
abstract: Integral membrane protein function can be modulated by the host bilayer. Because biological membranes are diverse and nonuniform, we explore the consequences of lipid diversity using gramicidin A channels embedded in phosphatidylcholine (PC) bilayers composed of equimolar mixtures of di-oleoyl-PC and di-erucoyl-PC (dC18:1+dC22:1, respectively), di-palmitoleoyl-PC and di-nervonoyl-PC (dC16:1+dC24:1, respectively), and di-eicosenoyl-PC (pure dC20:1), all of which have the same average bilayer chain length. Single-channel lifetime experiments, molecular dynamics simulations, and a simple lipid compression model are used in tandem to gain insight into lipid redistribution around the channel, which partially alleviates the bilayer deformation energy associated with channel formation. The average single-channel lifetimes in the two-component bilayers (95 ± 10 ms for dC18:1+dC22:1and 195 ± 20 ms for dC16:1+dC24:1) were increased relative to the single-component dC20:1control bilayer (65 ± 10 ms), implying lipid redistribution. Using a theoretical treatment of thickness-dependent changes in channel lifetimes, the effective local enrichment of lipids around the channel was estimated to be 58 ± 4% dC18:1and 66 ± 2% dC16:1in the dC18:1+dC22:1and dC16:1+dC24:1bilayers, respectively. 3.5-μs molecular dynamics simulations show 66 ± 2% dC16:1in the first lipid shell around the channel in the dC16:1+dC24:1bilayer, but no significant redistribution (50 ± 4% dC18:1) in the dC18:1+dC22:1bilayer; these simulated values are within the 95% confidence intervals of the experimental averages. The strong preference for the better matching lipid (dC16:1) near the channel in the dC16:1+dC24:1mixture and lesser redistribution in the dC18:1+dC22:1mixture can be explained by the energetic cost associated with compressing the lipids to match the channel's hydrophobic length.
authors.affiliation: Department of Chemistry, The University of Kansas, Lawrence, Kansas.
authors.forename: Andrew H
authors.initials: AH
authors.lastname: Beaven
authors.affiliation: Department of Physiology and Biophysics, Weill Cornell Medical College, New York, New York.
authors.forename: Andreia M
authors.initials: AM
authors.lastname: Maer
authors.affiliation: Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland.
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Sodt
authors.affiliation: Department of Biological Sciences and Bioengineering Program, Lehigh University, Bethlehem, Pennsylvania.
authors.forename: Huan
authors.initials: H
authors.lastname: Rui
authors.affiliation: Laboratory of Computational Biology, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Richard W
authors.initials: RW
authors.lastname: Pastor
authors.affiliation: Department of Physiology and Biophysics, Weill Cornell Medical College, New York, New York. Electronic address: sparre@med.cornell.edu.
authors.forename: Olaf S
authors.initials: OS
authors.lastname: Andersen
authors.affiliation: Department of Biological Sciences and Bioengineering Program, Lehigh University, Bethlehem, Pennsylvania. Electronic address: wonpil@lehigh.edu.
authors.forename: Wonpil
authors.initials: W
authors.lastname: Im
mesh_terms: D004548:Elasticity; D006096:Gramicidin / Q000737:chemistry* / Q000378:metabolism*; D057927:Hydrophobic and Hydrophilic Interactions; D008051:Lipid Bilayers / Q000737:chemistry* / Q000378:metabolism*; D008958:Models, Molecular; D017433:Protein Structure, Secondary
chemical_list: D008051:Lipid Bilayers; D006096:Gramicidin