Amphiphile regulation of ion channel function by changes in the bilayer; springconstant
by Lundbaek, Jens A.; Koeppe II, R. Erdman; Andersen, Olaf S.
Many drugs are amphiphiles that, in addition to binding to a particular; targetprotein,adsorbtocellmembranelipidbilayersandalter; intrinsicbilayerphysicalproperties(e.g.,bilayerthickness,; monolayercurvature,andelasticmoduli).Suchchangescanmodulate; membraneproteinfunctionbyalteringtheenergeticcost(Delta; G(bilayer))ofbilayerdeformationsassociatedwithprotein; conformationalchangesthatinvolvetheprotein-bilayerinterface.But; amphiphileshavecomplexeffectsonthephysicalpropertiesoflipid; bilayers,meaningthatthenetchangeinDeltaG(bilayer)cannotbe; predictedfrommeasurementsofisolatedchangesinsuchproperties.; Thus,thebilayercontributiontothepromiscuousregulationof; membraneproteinsbydrugsandotheramphiphilesremainsunknown.To; overcomethisproblem,weusegramicidinA(gA)channelsasmolecular; forceprobestomeasuretheneteffectofamphiphiles,at; concentrationsoftenusedinbiologicalresearch,onthebilayer; elasticresponsetoachangeinthehydrophobiclengthofanembedded; protein.Theeffectsofstructurallydiverseamphiphilescanbe; describedbychangesinaphenomenologicalbilayerspringconstant; (H-B)thatsummarizesthebilayerelasticproperties,assensedbya; bilayer-spanningprotein.Amphiphile-inducedchangesinH-B,measured; usinggAchannelsofaparticularlength,quantitativelypredict; changesinlifetimeforchannelsofadifferentlength-aswellas; changesintheinactivationofvoltage-dependentsodiumchannelsin; livingcells.TheuseofgAchannelsasmolecularforceprobesprovides; atoolforquantitative,predictivestudiesofbilayer-mediated; regulationofmembraneproteinfunctionbyamphiphiles.
- Journal
- Proceedings of the National Academy of Sciences of the United States of America
- Volume
- 107
- Issue
- 35
- Year
- 2010
- Start Page
- 15427
- ISBN/ISSN
- 1091-6490; 0027-8424
- PMID
- 20713738
- DOI
- 10.1073/pnas.1007455107