title: X-ray structure, thermodynamics, elastic properties and MD simulations of cardiolipin/dimyristoylphosphatidylcholine mixed membranes.
abstract: Cardiolipins (CLs) are important biologically for their unique role in biomembranes that couple phosphorylation and electron transport like bacterial plasma membranes, chromatophores, chloroplasts and mitochondria. CLs are often tightly coupled to proteins involved in oxidative phosphorylation. The first step in understanding the interaction of CL with proteins is to obtain the pure CL structure, and the structure of mixtures of CL with other lipids. In this work we use a variety of techniques to characterize the fluid phase 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, the bending modulus, KC, and SXray, a measure of chain orientational order. Our results reveal that TMCL thickens DMPC bilayers at all mole percentages, with a total increase of ∼6 Å in pure TMCL, and increases AL from 64 Å(2) (DMPC at 35 °C) to 109 Å(2) (TMCL at 50 °C). KC increases by ∼50%, indicating that TMCL stiffens DMPC membranes. TMCL also orders DMPC chains by a factor of ∼2 for pure TMCL. Coarse grain molecular dynamics simulations confirm the experimental thickening of 2 Å for 20mol% TMCL and locate the TMCL headgroups near the glycerol-carbonyl region of DMPC; i.e., they are sequestered below the DMPC phosphocholine headgroup. Our results suggest that TMCL plays a role similar to cholesterol in that it thickens and 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. Differential scanning calorimetry, SXray and CGMD simulations all suggest that TMCL does not form domains within the DMPC bilayers. We also determined the gel phase structure of TMCL, which surprisingly displays diffuse X-ray scattering, like a fluid phase lipid. AL=40.8 Å(2) for the ½TMCL gel phase, smaller than the DMPC gel phase with AL=47.2 Å(2), but similar to AL of DLPE=41 Å(2), consistent with untilted chains in gel phase TMCL.
authors.affiliation: Biological Physics Group, Physics Department, Carnegie Mellon University, Pittsburgh, PA 15213, United States.
authors.forename: Alexander L
authors.initials: AL
authors.lastname: Boscia
authors.affiliation: Biological Physics Group, Physics Department, Carnegie Mellon University, Pittsburgh, PA 15213, United States.
authors.forename: Bradley W
authors.initials: BW
authors.lastname: Treece
authors.affiliation: Bioengineering Department, University of Pittsburgh, Pittsburgh, PA 15260, United States.
authors.forename: Dariush
authors.initials: D
authors.lastname: Mohammadyani
authors.affiliation: Metabolic & Vascular Health, Medical School, University of Warwick, Coventry, England CV4 7AL, United Kingdom.
authors.forename: Judith
authors.initials: J
authors.lastname: Klein-Seetharaman
authors.affiliation: Department of Biomedical Engineering, University of Minnesota, Minneapolis, MN 55455, United States.
authors.forename: Anthony R
authors.initials: AR
authors.lastname: Braun
authors.affiliation: Groningen Biomolecular Sciences and Biotechnology Institute and Zernike Institute for Advanced Materials, University of Groningen, Nijenborgh 7, 9747 AG Groningen, The Netherlands.
authors.forename: Tsjerk A
authors.initials: TA
authors.lastname: Wassenaar
authors.affiliation: Department of Physics, Chemistry and Pharmacy, University of Southern Denmark, DK-5230 Odense M, Denmark.
authors.forename: Beate
authors.initials: B
authors.lastname: Klösgen
authors.affiliation: Biological Physics Group, Physics Department, Carnegie Mellon University, Pittsburgh, PA 15213, United States. Electronic address: stn@cmu.edu.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Tristram-Nagle
mesh_terms: D002152:Calorimetry, Differential Scanning; D002308:Cardiolipins / Q000737:chemistry*; D018360:Crystallography, X-Ray; D004134:Dimyristoylphosphatidylcholine / Q000737:chemistry* / Q000378:metabolism; D005782:Gels / Q000737:chemistry; D008051:Lipid Bilayers / Q000737:chemistry* / Q000378:metabolism; D008968:Molecular Conformation; D056004:Molecular Dynamics Simulation; D013816:Thermodynamics; D044366:Transition Temperature
chemical_list: D002308:Cardiolipins; D005782:Gels; D008051:Lipid Bilayers; D004134:Dimyristoylphosphatidylcholine
keywords: CGMD; CHESS; CL; Cornell High Energy Synchrotron Source; DLPE; DMPC; DMPE; DPPC; DPPE; DSC; Differential scanning calorimetry; IMMs; LAXS; Lipid bilayer structure; MLVs; NPT; NVT; PC; TFE; TMCL; WAXS; X-ray diffuse scattering; canonical ensemble (N, number of moles, V, volume, T, temperature, all conserved); cardiolipin; coarse grain molecular dynamics; differential scanning calorimetry; dilauroylphosphocholine; dimyristoylphosphocholine; dipalmitoylphosphocholine; dipalmitoylphosphoethanolamine; inner mitochondrial membranes; isobaric–isothermal ensemble; low-angle X-ray scattering; multilamellar vesicles; phosphocholine; tetramyristoylcardiolipin; trifluoroethanol; wide-angle X-ray scattering; ½TMCL