Boscia, Alexander L., Treece, Bradley W., Mohammadyani, Dariush, Klein-Seetharaman, Judith, Braun, Anthony R., Wassenaar, Tsjerk A., Klösgen, Beate and Tristram-Nagle, Stephanie (2014) X-ray structure, thermodynamics, elastic properties and MD simulations of cardiolipin/dimyristoylphosphatidylcholine mixed membranes. Chemistry and Physics of Lipids, Volume 178 . pp. 1-10. doi:10.1016/j.chemphyslip.2013.12.010

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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, 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 Å2 for the ½TMCL 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.

Item Type:	Journal Article
Divisions:	Faculty of Medicine > Warwick Medical School > Biomedical Sciences > Translational & Experimental Medicine > Metabolic and Vascular Health (- until July 2016) Faculty of Medicine > Warwick Medical School Faculty of Medicine > Warwick Medical School > Biomedical Sciences > Translational & Experimental Medicine
Journal or Publication Title:	Chemistry and Physics of Lipids
Publisher:	Elsevier Ireland Ltd
ISSN:	0009-3084
Official Date:	February 2014
Dates:	Date Event February 2014 Published 28 December 2013 Available 20 December 2013 Accepted 5 November 2013 Submitted
Volume:	Volume 178
Page Range:	pp. 1-10
DOI:	10.1016/j.chemphyslip.2013.12.010
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Restricted or Subscription Access

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