Carnegie Mellon University
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X-ray structure, thermodynamics, elastic properties and MDsimulations of cardiolipin/dimyristoylphosphatidylcholine mixedmembranes

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journal contribution
posted on 2014-01-01, 00:00 authored by Alex Boscia, Bradley W. Treece, Dariush Mohammadyani, Judith Klein-Seetharaman, Anthony R. Braun, Beate Kloesgen, Tsjerk A. Wassenaar, Stephanie Tristram-NagleStephanie Tristram-Nagle
tCardiolipins (CLs) are important biologically for their unique role in biomembranes that couple phos-phorylation and electron transport like bacterial plasma membranes, chromatophores, chloroplasts andmitochondria. CLs are often tightly coupled to proteins involved in oxidative phosphorylation. The firststep in understanding the interaction of CL with proteins is to obtain the pure CL structure, and the struc-ture of mixtures of CL with other lipids. In this work we use a variety of techniques to characterize the fluidphase structure, material properties and thermodynamics of mixtures of dimyristoylphosphatidylcholine(DMPC) with tetramyristoylcardiolipin (TMCL), both with 14-carbon chains, at several mole percentages.X-ray diffuse scattering was used to determine structure, including bilayer thickness and area/lipid, thebending modulus, KC, and SXray, a measure of chain orientational order. Our results reveal that TMCL thick-ens DMPC bilayers at all mole percentages, with a total increase of ∼6˚A in pure TMCL, and increases ALfrom 64˚ A2(DMPC at 35◦C) to 109˚A2(TMCL at 50◦C). KCincreases by ∼50%, indicating that TMCL stiffensDMPC membranes. TMCL also orders DMPC chains by a factor of ∼2 for pure TMCL. Coarse grain moleculardynamics simulations confirm the experimental thickening of 2˚A for 20 mol% TMCL and locate the TMCLheadgroups near the glycerol-carbonyl region of DMPC; i.e., they are sequestered below the DMPC phos-phocholine headgroup. Our results suggest that TMCL plays a role similar to cholesterol in that it thickensand stiffens DMPC membranes, orders chains, and is positioned under the umbrella of the PC headgroup.CL may be necessary for hydrophobic matching to inner mitochondrial membrane proteins. Differentialscanning calorimetry, SXrayand CGMD simulations all suggest that TMCL does not form domains withinthe DMPC bilayers. We also determined the gel phase structure of TMCL, which surprisingly displaysdiffuse X-ray scattering, like a fluid phase lipid. AL= 40.8˚ A2for the ½TMCL gel phase, smaller than theDMPC gel phase with AL= 47.2˚ A2, but similar to ALof DLPE = 41˚ A2, consistent with untilted chains in gelphase TMCL.




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