Gramicidin A Channel Formation Induces Local Lipid Redistribution I: Experiment and Simulation

被引：46

作者：

Beaven, Andrew H. ^{[1
]}

Maer, Andreia M. ^{[2
]}

Sodt, Alexander J. ^{[3
]}

Rui, Huan ^{[4
,5
]}

Pastor, Richard W. ^{[6
]}

Andersen, Olaf S. ^{[2
]}

Im, Wonpil ^{[4
,5
]}

机构：

[1] Univ Kansas, Dept Chem, Lawrence, KS 66045 USA

[2] Weill Cornell Med Coll, Dept Physiol & Biophys, New York, NY 10065 USA

[3] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA

[4] Lehigh Univ, Dept Biol Sci, Bethlehem, PA 18015 USA

[5] Lehigh Univ, Bioengn Program, Bethlehem, PA 18015 USA

[6] NHLBI, Lab Computat Biol, NIH, Bldg 10, Bethesda, MD 20892 USA

来源：

BIOPHYSICAL JOURNAL | 2017年 / 112卷 / 06期

基金：

美国国家卫生研究院; 美国国家科学基金会;

关键词：

CALCIUM ADENOSINE-TRIPHOSPHATASE; MOLECULAR-DYNAMICS; HYDROPHOBIC MISMATCH; BILAYER THICKNESS; FREE-ENERGY; MODEL MEMBRANES; CONDUCTANCE HETEROGENEITY; TRANSMEMBRANE PEPTIDE; PROTEIN INTERACTIONS; MIXED BILAYERS;

D O I：

10.1016/j.bpj.2017.01.028

中图分类号：

Q6 [生物物理学];

学科分类号：

071011 ;

摘要：

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 (dC(18: 1)+dC(22: 1), respectively), di-palmitoleoyl- PC and di-nervonoyl-PC (dC(16: 1)+dC(24: 1), respectively), and di-eicosenoyl-PC (pure dC(20: 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 dC(18: 1)+dC(22: 1) and 195 +/- 20 ms for dC(16: 1)+dC(24: 1)) were increased relative to the single-component dC(20: 1) control bilayer (65510 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 5854% dC(18: 1) and 6652% dC(16: 1) in the dC(18: 1)+dC(22: 1) and dC(16: 1)+dC(24: 1) bilayers, respectively. 3.5-ms molecular dynamics simulations show 66 +/- 2% dC16: 1 in the first lipid shell around the channel in the dC(16: 1)+dC(24: 1) bilayer, but no significant redistribution (50 +/- 4% dC18: 1) in the dC(18: 1)+dC(22: 1) bilayer; these simulated values are within the 95% confidence intervals of the experimental averages. The strong preference for the better matching lipid (dC(16: 1)) near the channel in the dC(16: 1)+dC(24: 1) mixture and lesser redistribution in the dC(18: 1)+dC(22: 1) mixture can be explained by the energetic cost associated with compressing the lipids to match the channel's hydrophobic length.

引用

页码：1185 / 1197

页数：13

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