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

Andrew H. Beaven, Andreia M. Maer, Alexander J. Sodt, Huan Rui, Richard W. Pastor, Olaf S. Andersen, Wonpil Im

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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+dC22:1 and 195 ± 20 ms for dC16:1+dC24:1) were increased relative to the single-component dC20:1 control 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% dC18:1 and 66 ± 2% dC16:1 in the dC18:1+dC22:1 and dC16:1+dC24:1 bilayers, respectively. 3.5-μs molecular dynamics simulations show 66 ± 2% dC16:1 in the first lipid shell around the channel in the dC16:1+dC24:1 bilayer, but no significant redistribution (50 ± 4% dC18:1) in the dC18:1+dC22:1 bilayer; 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+dC24:1 mixture and lesser redistribution in the dC18:1+dC22:1 mixture can be explained by the energetic cost associated with compressing the lipids to match the channel's hydrophobic length.

Original languageEnglish (US)
Pages (from-to)1185-1197
Number of pages13
JournalBiophysical journal
Volume112
Issue number6
DOIs
StatePublished - Mar 28 2017

Bibliographical note

Funding Information:
This work was supported in part by the National Science Foundation (MCB-1157677 and MCB-1727508 to W.I.), XSEDE Resources (MCB070009 to W.I.), the National Institutes of Health (GM021342 to O.S.A. and GM087519 to W.I.), and the Intramural Research Program of the National Institutes of Health, National Heart, Lung and Blood Institute using the high performance computational capabilities (LoBoS cluster) at the National Institutes of Health, Bethesda, MD (R.W.P. and A.J.S.). Anton computer time was provided by the National Center for Multiscale Modeling of Biological Systems through grant No. P41GM103712-S1 from the National Institutes of Health and the Pittsburgh Supercomputing Center.

Publisher Copyright:
© 2017 Biophysical Society

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