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European Biophysics Journal

, Volume 41, Issue 10, pp 875–890 | Cite as

Model-based approaches for the determination of lipid bilayer structure from small-angle neutron and X-ray scattering data

  • Frederick A. Heberle
  • Jianjun Pan
  • Robert F. Standaert
  • Paul Drazba
  • Norbert Kučerka
  • John Katsaras
Review

Abstract

Some of our recent work has resulted in the detailed structures of fully hydrated, fluid phase phosphatidylcholine (PC) and phosphatidylglycerol (PG) bilayers. These structures were obtained from the joint refinement of small-angle neutron and X-ray data using the scattering density profile (SDP) models developed by Kučerka et al. (Biophys J 95:2356–2367, 2008; J Phys Chem B 116:232–239, 2012). In this review, we first discuss models for the standalone analysis of neutron or X-ray scattering data from bilayers, and assess the strengths and weaknesses inherent to these models. In particular, it is recognized that standalone data do not contain enough information to fully resolve the structure of naturally disordered fluid bilayers, and therefore may not provide a robust determination of bilayer structure parameters, including the much-sought-after area per lipid. We then discuss the development of matter density-based models (including the SDP model) that allow for the joint refinement of different contrast neutron and X-ray data, as well as the implementation of local volume conservation within the unit cell (i.e., ideal packing). Such models provide natural definitions of bilayer thicknesses (most importantly the hydrophobic and Luzzati thicknesses) in terms of Gibbs dividing surfaces, and thus allow for the robust determination of lipid areas through equivalent slab relationships between bilayer thickness and lipid volume. In the final section of this review, we discuss some of the significant findings/features pertaining to structures of PC and PG bilayers as determined from SDP model analyses.

Keywords

Lipid bilayer Bilayer structure Area per lipid Bilayer thickness Molecular dynamics simulations Fluid phase 

Notes

Acknowledgments

This work acknowledges the support of the office of Biological and Environmental Research (BER) at Oak Ridge National Laboratory’s (ORNL) Center for Structural Molecular Biology (CSMB) through the utilization of facilities supported by the US Department of Energy, managed by UT-Battelle, LLC under contract no. DE-AC05-00OR2275. Facilities located at the National Institute of Standards and Technology (NIST) are supported in part by the National Science Foundation under agreement no. DMR- 0944772. Facilities located at the Cornell High Energy Synchrotron Source (CHESS) are supported by the National Science Foundation and the National Institutes of Health/National Institute of General Medical Sciences under National Science Foundation award DMR-0225180. JK is supported by ORNL’s Program Development (PD) and Laboratory Directed Research and Development (LDRD) programs. RFS is supported by ORNL’s LDRD program.

References

  1. Anezo C, de Vries AH, Holtje HD, Tieleman DP, Marrink SJ (2003) Methodological issues in lipid bilayer simulations. J Phys Chem B 107:9424–9433CrossRefGoogle Scholar
  2. Armen RS, Uitto OD, Feller SE (1998) Phospholipid component volumes: determination and application to bilayer structure calculations. Biophys J 75:734–744PubMedCrossRefGoogle Scholar
  3. Balgavý P, Dubničková M, Kučerka N, Kiselev MA, Yaradaikin SP, Uhríková D (2001) Bilayer thickness and lipid interface area in unilamellar extruded 1,2-diacylphosphatidylcholine liposomes: a small-angle neutron scattering study. Biochim Biophys Acta 1512:40–52PubMedCrossRefGoogle Scholar
  4. Bangham AD, Standish MM, Watkins JC (1965) Diffusion of univalent ions across the lamellae of swollen phospholipids. J Mol Biol 13:238–252PubMedCrossRefGoogle Scholar
  5. Brezesinski G, Dietrich A, Struth B, Bohm C, Bouwman WG, Kjaer K, Mohwald H (1995) Influence of ether linkages on the structure of double-chain phospholipid monolayers. Chem Phys Lipids 76:145–157CrossRefGoogle Scholar
  6. Büldt G, Gally HU, Seelig A, Seelig J, Zaccai G (1978) Neutron diffraction studies on selectively deuterated phospholipid bilayers. Nature 271:182–184PubMedCrossRefGoogle Scholar
  7. Büldt G, Gally HU, Seelig J, Zaccai G (1979) Neutron diffraction studies on phosphatidylcholine model membranes. I. Head group conformation. J Mol Biol 134:673–691PubMedCrossRefGoogle Scholar
  8. Devrije T, Deswart RL, Dowhan W, Tommassen J, Dekruijff B (1988) Phosphatidylglycerol is involved in protein translocation across Escherichia-coli inner membranes. Nature 334:173–175CrossRefGoogle Scholar
  9. Elmore DE (2006) Molecular dynamics simulation of a phosphatidylglycerol membrane. FEBS Lett 580:144–148PubMedCrossRefGoogle Scholar
  10. Franks NP, Melchior V, Kirshner DA, Caspar DL (1982) Structure of myelin lipid bilayers. Changes during maturation. J Mol Biol 155:133–153PubMedCrossRefGoogle Scholar
  11. Greenwood AI, Pan J, Mills TT, Nagle JF, Epand RM, Tristram-Nagle S (2008) CRAC motif peptide of the HIV-1 gp41 protein thins SOPC membranes and interacts with cholesterol. Biochem Biophys Acta 1778:1120–1130PubMedCrossRefGoogle Scholar
  12. Guler SD, Ghosh DD, Pan JJ, Mathai JC, Zeidel ML, Nagle JF, Tristram-Nagle S (2009) Effects of ether vs. ester linkage on lipid bilayer structure and water permeability. Chem Phys Lipids 160:33–44PubMedCrossRefGoogle Scholar
  13. Gulik-Krzywicki T, Rivas E, Luzzati V (1967) Structure and polymorphism of lipids: X-ray diffraction study of the system formed from beef heart mitochondria lipids and water. J Mol Biol 27:303–322PubMedCrossRefGoogle Scholar
  14. Hannun YA, Obeid LM (2008) Principles of bioactive lipid signalling: lessons from sphingolipids. Nat Rev Mol Cell Bio 9:139–150CrossRefGoogle Scholar
  15. Hazel JR (1995) Thermal adaptation in biological-membranes—is homeoviscous adaptation the explanation? Annu Rev Physiol 57:19–42PubMedCrossRefGoogle Scholar
  16. Henin J, Shinoda W, Klein ML (2009) Models for phosphatidylglycerol lipids put to a structural test. J Phys Chem B 113:6958–6963PubMedCrossRefGoogle Scholar
  17. Hope MJ, Bally MB, Mayer LD, Janoff AS, Cullis PR (1986) Generation of multilamellar and unilamellar phospholipid vesicles. Chem Phys Lipids 40:89–107CrossRefGoogle Scholar
  18. Hristova K, White SH (1998) Determination of the hydrocarbon core structure of fluid dioleoylphosphocholine (DOPC) bilayers by x-ray diffraction using specific bromination of the double-bonds: effect of hydration. Biophys J 74:2419–2433PubMedCrossRefGoogle Scholar
  19. Huang C (1969) Studies on phosphatidylcholine vesicles. Formation and physical characteristics. Biochemistry 8:344–352PubMedCrossRefGoogle Scholar
  20. Karlovská J, Uhríková D, Kučerka N, Teixeira J, Devínsky F, Lacko I, Balgavý P (2006) Influence of N-dodecyl-N,N-dimethylamine N-oxide on the activity of sarcoplasmic reticulum Ca2+-transporting ATPase reconstituted into diacylphosphatidylcholine vesicles: effects of bilayer physical parameters. Biophys Chem 119:69–77PubMedCrossRefGoogle Scholar
  21. Katsaras J (1997) Highly aligned lipid membrane systems in the physiologically relevant “excess water” condition. Biophys J 73:2924–2929PubMedCrossRefGoogle Scholar
  22. Katsaras J (1998) Adsorbed to a rigid substrate, dimyristoylphosphatidylcholine multibilayers attain full hydration in all mesophases. Biophys J 75:2157–2162PubMedCrossRefGoogle Scholar
  23. Katsaras J, Stinson RH (1990) High-resolution electron-density profiles reveal influence of fatty-acids on bilayer structure. Biophys J 57:649–655PubMedCrossRefGoogle Scholar
  24. Katsaras J, Watson MJ (2000) Sample cell capable of 100 % relative humidity suitable for X-ray diffraction of aligned lipid multibilayers. Rev Sci Instrum 71:1737–1739CrossRefGoogle Scholar
  25. Katsaras J, Raghunathan VA, Dufourc EJ, Dufourcq J (1995) Evidence for a two-dimensional molecular lattice in subgel phase DPPC bilayers. Biochemistry 34:4684–4688PubMedCrossRefGoogle Scholar
  26. Katsaras J, Tristram-Nagle S, Liu Y, Headrick RL, Fontes E, Mason PC, Nagle JF (2000) Clarification of the ripple phase of lecithin bilayers using fully hydrated, aligned samples. Phys Rev E 61:5668–5677CrossRefGoogle Scholar
  27. King GI, White SH (1986) Determining bilayer hydrocarbon thickness from neutron diffraction measurements using strip-function models. Biophys J 49:1047–1054PubMedCrossRefGoogle Scholar
  28. Kiselev MA, Lesieur P, Kisselev AM, Lombardo D, Aksenov VL (2002) Model of separated form factors for unilamellar vesicles. Appl Phys A 74:S1654–S1656CrossRefGoogle Scholar
  29. Kiselev MA, Zemlyanaya EV, Aswal VK, Neubert RH (2006) What can we learn about the lipid vesicle structure from the small-angle neutron scattering experiment? Eur Biophys J 35:477–493PubMedCrossRefGoogle Scholar
  30. Klauda JB, Brooks BR, MacKerell AD, Venable RM, Pastor RW (2005) An ab initio study on the torsional surface of alkanes and its effect on molecular simulations of alkanes and a DPPC bilayer. J Phys Chem B 109:5300–5311PubMedCrossRefGoogle Scholar
  31. Klauda JB, Kučerka N, Brooks BR, Pastor RW, Nagle JF (2006) Simulation-based methods for interpreting X-ray data from lipid bilayers. Biophys J 90:2796–2807PubMedCrossRefGoogle Scholar
  32. Kučerka N, Nagle JF, Feller SE, Balgavy P (2004) Models to analyze small-angle neutron scattering from unilamellar lipid vesicles. Phys Rev E 69:051903CrossRefGoogle Scholar
  33. Kučerka N, Tristram-Nagle S, Nagle JF (2005) Structure of fully hydrated fluid phase lipid bilayers with monounsaturated chains. J Membr Biol 208:193–202PubMedGoogle Scholar
  34. Kučerka N, Pencer J, Nieh MP, Katsaras J (2007a) Influence of cholesterol on the bilayer properties of monounsaturated phosphatidylcholine unilamellar vesicles. Eur Phys J E Soft Matter 23:247–254PubMedCrossRefGoogle Scholar
  35. Kučerka N, Pencer J, Sachs JN, Nagle JF, Katsaras J (2007b) Curvature effect on the structure of phospholipid bilayers. Langmuir 23:1292–1299PubMedCrossRefGoogle Scholar
  36. Kučerka N, Nagle JF, Sachs JN, Feller SE, Pencer J, Jackson A, Katsaras J (2008) Lipid bilayer structure determined by the simultaneous analysis of neutron and X-ray scattering data. Biophys J 95:2356–2367PubMedCrossRefGoogle Scholar
  37. Kučerka N, Gallova J, Uhrikova D, Balgavy P, Bulacu M, Marrink SJ, Katsaras J (2009) Areas of monounsaturated diacylphosphatidylcholines. Biophys J 97:1926–1932PubMedCrossRefGoogle Scholar
  38. Kučerka N, Katsaras J, Nagle JF (2010) Comparing membrane simulations to scattering experiments: introducing the SIMtoEXP software. J Membr Biol 235:43–50PubMedCrossRefGoogle Scholar
  39. Kučerka N, Nieh MP, Katsaras J (2011) Fluid phase lipid areas and bilayer thicknesses of commonly used phosphatidylcholines as a function of temperature. Biochim Biophys Acta 1808:2761–2771PubMedCrossRefGoogle Scholar
  40. Kučerka N, Holland BW, Gray CG, Tomberli B, Katsaras J (2012) Scattering density profile model of POPG bilayers as determined by molecular dynamics simulations and small-angle neutron and X-ray scattering experiments. J Phys Chem B 116:232–239PubMedCrossRefGoogle Scholar
  41. Leftin A, Brown MF (2011) An NMR database for simulations of membrane dynamics. Biochim Biophys Acta 1808:818–839PubMedCrossRefGoogle Scholar
  42. Lemmich J, Mortensen K, Ipsen JH, Honger T, Bauer R, Mouritsen OG (1996) Small-angle neutron scattering from multilamellar lipid bilayers: theory, model, and experiment. Phys Rev E 53:5169–5180CrossRefGoogle Scholar
  43. Levine YK, Wilkins MH (1971) Structure of oriented lipid bilayers. Nat New Biol 230:69–72PubMedCrossRefGoogle Scholar
  44. Lingwood D, Simons K (2010) Lipid rafts as a membrane-organizing principle. Science 327:46–50PubMedCrossRefGoogle Scholar
  45. Liu YF, Nagle JF (2004) Diffuse scattering provides material parameters and electron density profiles of biomembranes. Phys Rev E 69:040901(R)Google Scholar
  46. Lyatskaya Y, Liu Y, Tristram-Nagle S, Katsaras J, Nagle JF (2001) Method for obtaining structure and interactions from oriented lipid bilayers. Phys Rev E 63:011907CrossRefGoogle Scholar
  47. Marrink SJ, Risselada HJ, Yefimov S, Tieleman DP, de Vries AH (2007) The MARTINI force field: coarse grained model for biomolecular simulations. J Phys Chem B 111:7812–7824PubMedCrossRefGoogle Scholar
  48. Mason PC, Gaulin BD, Epand RM, Wignall GD, Lin JS (1999) Small angle neutron scattering and calorimetric studies of large unilamellar vesicles of the phospholipid dipalmitoylphosphatidylcholine. Phys Rev E 59:3361–3367CrossRefGoogle Scholar
  49. McDaniel RV, McIntosh TJ (1986) X-ray diffraction studies of the cholera toxin receptor, GM1. Biophys J 49:94–96PubMedCrossRefGoogle Scholar
  50. McIntosh TJ, Holloway PW (1987) Determination of the depth of bromine atoms in bilayers formed from bromolipid probes. Biochemistry 26:1783–1788PubMedCrossRefGoogle Scholar
  51. Nagle JF, Tristram-Nagle S (2000a) Lipid bilayer structure. Curr Opin Struct Biol 10:474–480PubMedCrossRefGoogle Scholar
  52. Nagle JF, Tristram-Nagle S (2000b) Structure of lipid bilayers. Biochim Biophys Acta Rev Biomembr 1469:159–195CrossRefGoogle Scholar
  53. Nikaido H, Vaara M (1985) Molecular-basis of bacterial outer-membrane permeability. Microbiol Rev 49:1–32PubMedGoogle Scholar
  54. Obrien FEM (1948) The control of humidity by saturated salt solutions. J Sci Instrum Phys Ind 25:73–76Google Scholar
  55. Pabst G, Rappolt M, Amenitsch H, Laggner P (2000) Structural information from multilamellar liposomes at full hydration: full q-range fitting with high quality x-ray data. Phys Rev E 62:4000–4009CrossRefGoogle Scholar
  56. Pan J, Tristram-Nagle S, Kučerka N, Nagle JF (2008) Temperature dependence of structure, bending rigidity, and bilayer interactions of dioleoylphosphatidylcholine bilayers. Biophys J 94:117–124PubMedCrossRefGoogle Scholar
  57. Pan J, Tieleman DP, Nagle JF, Kučerka N, Tristram-Nagle S (2009) Alamethicin in lipid bilayers: combined use of X-ray scattering and MD simulations. Biochem Biophys Acta 1788:1387–1397PubMedCrossRefGoogle Scholar
  58. Pan J, Heberle FA, Kučerka N, Tristram-Nagle S, Szymanski M, Koepfinger M, Katsaras J (2012) Molecular structure of phosphatidylglycerol bilayers: fluid phase lipid areas and bilayer thicknesses as a function of temperature. Biophys J 102:504aGoogle Scholar
  59. Pencer J, Hallett FR (2000) Small-angle neutron scattering from large unilamellar vesicles: an improved method for membrane thickness determination. Phys Rev E 61:3003–3008CrossRefGoogle Scholar
  60. Pencer J, Nieh MP, Harroun TA, Krueger S, Adams C, Katsaras J (2005) Bilayer thickness and thermal response of dimyristoylphosphatidylcholine unilamellar vesicles containing cholesterol, ergosterol and lanosterol: a small-angle neutron scattering study. Biochim Biophys Acta 1720:84–91PubMedCrossRefGoogle Scholar
  61. Pencer J, Krueger S, Adams CP, Katsaras J (2006) Method of separated form factors for polydisperse vesicles. J Appl Crystallogr 39:293–303CrossRefGoogle Scholar
  62. Petrache HI, Feller SE, Nagle JF (1997) Determination of component volumes of lipid bilayers from simulations. Biophys J 72:2237–2242PubMedCrossRefGoogle Scholar
  63. Petrache HI, Dodd SW, Brown MF (2000) Area per lipid and acyl length distributions in fluid phosphatidylcholines determined by (2)H NMR spectroscopy. Biophys J 79:3172–3192PubMedCrossRefGoogle Scholar
  64. Qian S, Heller WT (2011) Peptide-induced asymmetric distribution of charged lipids in a vesicle bilayer revealed by small-angle neutron scattering. J Phys Chem B 115:9831–9837PubMedCrossRefGoogle Scholar
  65. Raghunathan VA, Katsaras J (1995) Structure of the Lc′ phase in a hydrated lipid multilamellar system. Phys Rev Lett 74:4456–4459PubMedCrossRefGoogle Scholar
  66. Rand RP, Luzzati V (1968) X-ray diffraction study in water of lipids extracted from human erythrocytes: the position of cholesterol in the lipid lamellae. Biophys J 8:125–137PubMedCrossRefGoogle Scholar
  67. Rand RP, Parsegian VA (1989) Hydration forces between phospholipid-bilayers. Biochim Biophys Acta 988:351–376CrossRefGoogle Scholar
  68. Riske KA, Amaral LQ, Lamy-Freund MT (2001) Thermal transitions of DMPG bilayers in aqueous solution: SAXS structural studies. Biochim Biophys Acta 1511:297–308PubMedCrossRefGoogle Scholar
  69. Schalke M, Kruger P, Weygand M, Losche M (2000) Submolecular organization of DMPA in surface monolayers: beyond the two-layer model. Biochim Biophys Acta 1464:113–126PubMedCrossRefGoogle Scholar
  70. Seddon AM, Lorch M, Ces O, Templer RH, Macrae F, Booth PJ (2008) Phosphatidylglycerol lipids enhance folding of an alpha helical membrane protein. J Mol Biol 380:548–556PubMedCrossRefGoogle Scholar
  71. Shekhar P, Nanda H, Losche M, Heinrich F (2011) Continuous distribution model for the investigation of complex molecular architectures near interfaces with scattering techniques. J Appl Phys 110:102216–10221612PubMedCrossRefGoogle Scholar
  72. Shoemaker SD, Vanderlick TK (2002) Intramembrane electrostatic interactions destabilize lipid vesicles. Biophys J 83:2007–2014PubMedCrossRefGoogle Scholar
  73. Singer SJ, Nicolson GL (1972) Fluid mosaic model of the structure of cell-membranes. Science 175:720–731PubMedCrossRefGoogle Scholar
  74. Spector AA, Yorek MA (1985) Membrane lipid composition and cellular function. J Lipid Res 26:1015–1035PubMedGoogle Scholar
  75. Sun WJ, Tristram-Nagle S, Suter RM, Nagle JF (1996) Structure of gel phase saturated lecithin bilayers: temperature and chain length dependence. Biophys J 71:885–891PubMedCrossRefGoogle Scholar
  76. Tenchov BG, Yanev TK, Tihova MG, Koynova RD (1985) A probability concept about size distributions of sonicated lipid vesicles. Biochim Biophys Acta 816:122–130PubMedCrossRefGoogle Scholar
  77. Tolokh IS, Vivcharuk V, Tomberli B, Gray CG (2009) Binding free energy and counterion release for adsorption of the antimicrobial peptide lactoferricin B on a POPG membrane. Phys Rev E 80:031911CrossRefGoogle Scholar
  78. Tristram-Nagle SA (2007) Preparation of oriented, fully hydrated lipid samples for structure determination using X-ray scattering. Methods Mol Biol 400:63–75PubMedCrossRefGoogle Scholar
  79. Tristram-Nagle S, Nagle JF (2004) Lipid bilayers: thermodynamics, structure, fluctuations, and interactions. Chem Phys Lipids 127:3–14PubMedCrossRefGoogle Scholar
  80. Tristram-Nagle S, Liu YF, Legleiter J, Nagle JF (2002) Structure of gel phase DMPC determined by X-ray diffraction. Biophys J 83:3324–3335PubMedCrossRefGoogle Scholar
  81. Tristram-Nagle S, Chan R, Kooijman E, Uppamoochikkal P, Qiang W, Weliky DP, Nagle JF (2010) HIV fusion peptide penetrates, disorders, and softens T-cell membrane mimics. J Mol Biol 402:139–153PubMedCrossRefGoogle Scholar
  82. van Meer G, de Kroon AI (2011) Lipid map of the mammalian cell. J Cell Sci 124:5–8PubMedCrossRefGoogle Scholar
  83. White SH, King GI (1985) Molecular packing and area compressibility of lipid bilayers. Proc Natl Acad Sci USA 82:6532–6536PubMedCrossRefGoogle Scholar
  84. Wiener MC, White SH (1992a) Structure of a fluid dioleoylphosphatidylcholine bilayer determined by joint refinement of X-ray and neutron diffraction data. II. Distribution and packing of terminal methyl groups. Biophys J 61:428–433PubMedCrossRefGoogle Scholar
  85. Wiener MC, White SH (1992b) Structure of a fluid dioleoylphosphatidylcholine bilayer determined by joint refinement of x-ray and neutron diffraction data. III. Complete structure. Biophys J 61:434–447PubMedCrossRefGoogle Scholar
  86. Wiener MC, Suter RM, Nagle JF (1989) Structure of the fully hydrated gel phase of dipalmitoylphosphatidylcholine. Biophys J 55:315–325PubMedCrossRefGoogle Scholar
  87. Wiener MC, King GI, White SH (1991) Structure of a fluid dioleoylphosphatidylcholine bilayer determined by joint refinement of x-ray and neutron diffraction data. I. Scaling of neutron data and the distributions of double bonds and water. Biophys J 60:568–576PubMedCrossRefGoogle Scholar
  88. Wilkins MHF, Blaurock AE, Engelman DM (1971) Bilayer structure in membranes. Nat New Biol 230:72–76PubMedCrossRefGoogle Scholar
  89. Worthington CR (1969) The interpretation of low-angle X-ray data from planar and concentric multilayered structures. The use of one-dimensional electron density strip models. Biophys J 9:222–234PubMedCrossRefGoogle Scholar
  90. Worthington CR (1981) The determination of the 1st-order phase in membrane diffraction using electron-density strip models. J Appl Crystallogr 14:387–391CrossRefGoogle Scholar
  91. Worthington CR, Blaurock AE (1969) A structural analysis of nerve myelin. Biophys J 9:970–990PubMedCrossRefGoogle Scholar
  92. Wymann MP, Schneiter R (2008) Lipid signalling in disease. Nat Rev Mol Cell Bio 9:162–176CrossRefGoogle Scholar
  93. Young JF (1967) Humidity control in the laboratory using salt solutions—a review. J Appl Chem 17:241–245CrossRefGoogle Scholar
  94. Zaccai G, Büldt G, Seelig A, Seelig J (1979) Neutron diffraction studies on phosphatidylcholine model membranes. II. Chain conformation and segmental disorder. J Mol Biol 134:693–706PubMedCrossRefGoogle Scholar
  95. Zhang YM, Rock CO (2008) Membrane lipid homeostasis in bacteria. Nat Rev Microbiol 6:222–233PubMedCrossRefGoogle Scholar
  96. Zhang R, Suter RM, Nagle JF (1994) Theory of the structure factor of lipid bilayers. Phys Rev E 50:5047–5060CrossRefGoogle Scholar
  97. Zhao W, Rog T, Gurtovenko AA, Vattulainen I, Karttunen M (2007) Atomic-scale structure and electrostatics of anionic palmitoyloleoylphosphatidylglycerol lipid bilayers with Na+ counterions. Biophys J 92:1114–1124PubMedCrossRefGoogle Scholar

Copyright information

© European Biophysical Societies' Association 2012

Authors and Affiliations

  • Frederick A. Heberle
    • 1
  • Jianjun Pan
    • 1
  • Robert F. Standaert
    • 2
    • 3
  • Paul Drazba
    • 4
  • Norbert Kučerka
    • 5
    • 6
  • John Katsaras
    • 1
    • 4
    • 5
    • 7
  1. 1.Biology and Soft Matter DivisionNeutron Sciences Directorate, Oak Ridge National LaboratoryOak RidgeUSA
  2. 2.Biosciences DivisionEnergy and Environmental Sciences Directorate, Oak Ridge National LaboratoryOak RidgeUSA
  3. 3.Department of Biochemistry and Molecular and Cellular BiologyThe University of TennesseeKnoxvilleUSA
  4. 4.Department of Physics and AstronomyThe University of TennesseeKnoxvilleUSA
  5. 5.Canadian Neutron Beam CentreNational Research CouncilChalk RiverCanada
  6. 6.Department of Physical Chemistry of DrugsFaculty of Pharmacy, Comenius UniversityBratislavaSlovakia
  7. 7.Joint Institute for Neutron SciencesOak Ridge National LaboratoryOak RidgeUSA

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