X-ray structure, thermodynamics, elastic properties and MD simulations of cardiolipin/dimyristoylphosphatidylcholine mixed membranes

Alexander L. Boscia, Bradley W. Treece, Dariush Mohammadyani, Judith Klein-Seetharaman, Anthony R. Braun, Tsjerk A. Wassenaar, Beate Klösgen, Stephanie Tristram-Nagle

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28 Scopus citations

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 Å2 (DMPC at 35 C) to 109 Å2 (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 20 mol% 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, S Xray 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 Å2 for the TMCL gel phase, smaller than the DMPC gel phase with AL = 47.2 Å2, but similar to AL of DLPE = 41 Å2, consistent with untilted chains in gel phase TMCL.

Original languageEnglish (US)
Pages (from-to)1-10
Number of pages10
JournalChemistry and Physics of Lipids
Volume178
DOIs
StatePublished - Feb 2014

Bibliographical note

Funding Information:
Research reported in this publication was supported by the National Institute of General Medical Sciences of the National Institutes of Health under award number R01GM44976 (AIB, BWT, and STN), NSF 1144281 (DM and JK-S), and NRSA pre-doctoral fellowship award number F31 NS077634-02 (ARB). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. A.I.B. was partially supported by the Howard Hughes Medical Institute (HHMI) for undergraduate research and by the Lipella Company, Pittsburgh, PA. We acknowledge the Cornell High Energy Synchrotron Source (CHESS), which is supported by the National Science Foundation (NSF) and the NIH/NIGMS under NSF award DMR-093684, and we especially thank Dr. Arthur Woll for facilitating our use of the G1 station. The authors would like to thank Thalia Mills for her help with the oriented sample preparation, Dave Bauer for his help with the VP-DSC data collection in the Evilevitch Lab, and Leah Langer for help in determining the number densities. The authors would like to thank Prof. John Nagle for helpful discussions.

Keywords

  • DMPC
  • Differential scanning calorimetry
  • LAXS
  • Lipid bilayer structure
  • WAXS
  • X-ray diffuse scattering

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