Cholesterol Effects on the Physical Properties of Lipid Membranes Viewed by Solid-state NMR Spectroscopy

  • Trivikram R. Molugu
  • Michael F. BrownEmail author
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1115)


In this chapter, we review the physical properties of lipid/cholesterol mixtures involving studies of model membranes using solid-state NMR spectroscopy. The approach allows one to quantify the average membrane structure, fluctuations, and elastic deformation upon cholesterol interaction. Emphasis is placed on understanding the membrane structural deformation and emergent fluctuations at an atomistic level. Lineshape measurements using solid-state NMR spectroscopy give equilibrium structural properties, while relaxation time measurements study the molecular dynamics over a wide timescale range. The equilibrium properties of glycerophospholipids, sphingolipids, and their binary and tertiary mixtures with cholesterol are accessible. Nonideal mixing of cholesterol with other lipids explains the occurrence of liquid-ordered domains. The entropic loss upon addition of cholesterol to sphingolipids is less than for glycerophospholipids, and may drive formation of lipid rafts. The functional dependence of 2H NMR spin–lattice relaxation (R1Z) rates on segmental order parameters (SCD) for lipid membranes is indicative of emergent viscoelastic properties. Addition of cholesterol shows stiffening of the bilayer relative to the pure lipids and this effect is diminished for lanosterol. Opposite influences of cholesterol and detergents on collective dynamics and elasticity at an atomistic scale can potentially affect lipid raft formation in cellular membranes.


Area per lipid Cholesterol Lanosterol Lipid rafts Membrane elasticity Solid-state NMR 



This research was supported by the US National Institutes of Health. The authors are grateful to the past and present members of our laboratory for their many outstanding contributions to the research in this chapter.


  1. 1.
    van Meer G, Voelker DR, Feigenson GW. Membrane lipids: where they are and how they behave. Nat Rev Mol Cell Biol. 2008;9:112–24.PubMedPubMedCentralGoogle Scholar
  2. 2.
    Krause MR, Regen SL. The structural role of cholesterol in cell membranes: from condensed bilayers to lipid rafts. Acc Chem Res. 2014;47:3512–21.PubMedCrossRefGoogle Scholar
  3. 3.
    Maxfield FR, Tabas I. Role of cholesterol and lipid organization in disease. Nature. 2005;438:612–21.PubMedCrossRefPubMedCentralGoogle Scholar
  4. 4.
    Yeagle PL. Modulation of membrane function by cholesterol. Biochimie. 1991;73:1303–10.PubMedCrossRefPubMedCentralGoogle Scholar
  5. 5.
    Brown MF. Modulation of rhodopsin function by properties of the membrane bilayer. Chem Phys Lipids. 1994;73:159–80.CrossRefGoogle Scholar
  6. 6.
    Brown MF. Curvature forces in membrane lipid-protein interactions. Biochemistry. 2012;51:9782–95.PubMedCrossRefPubMedCentralGoogle Scholar
  7. 7.
    Brown MF. Soft matter in lipid–protein interactions. Annu Rev Biophys. 2017;46:379–410.CrossRefGoogle Scholar
  8. 8.
    Sheng R, Chen Y, Gee HY, Stec E, Melowic HR, Blatner NR, Tun MP, Kim Y, Källberg M, Fujiwara TK, Hong JH, Kim KP, Lu H, Kusumi A, Lee MG, Cho W. Cholesterol modulates cell signaling and protein networking by specifically interacting with PDZ domain-containing scaffold proteins. Nat Commun. 2012;3:1249.PubMedCrossRefPubMedCentralGoogle Scholar
  9. 9.
    Huang P, Nedelcu D, Watanabe M, Jao C, Kim Y, Liu J, Salic A. Cellular cholesterol directly activates smoothened in Hedgehog signaling. Cell. 2016;166:1176–87.PubMedCrossRefPubMedCentralGoogle Scholar
  10. 10.
    Liu S-L, Sheng R, Jung JH, Wang L, Stec E, O'Connor MJ, Song S, Bikkavilli RK, Winn RA, Lee D, Baek K, Ueda K, Levitan I, Kim K-P, Cho W. Orthogonal lipid sensors identify transbilayer asymmetry of plasma membrane cholesterol. Nature Chem Biol. 2016;13:268–74.CrossRefGoogle Scholar
  11. 11.
    Molugu TR, Brown MF. Cholesterol-induced suppression of membrane elastic fluctuations at the atomistic level. Chem Phys Lipids. 2016;199:39–51.PubMedCrossRefPubMedCentralGoogle Scholar
  12. 12.
    Arriaga LR, Rodriguez-Garcia R, Moleiro LH, Prevost S, Lopez-Montero I, Hellweg T, Monroy F. Dissipative dynamics of fluid lipid membranes enriched in cholesterol. Adv Colloid Interface Sci. 2017;247:514–20.PubMedCrossRefGoogle Scholar
  13. 13.
    Seddon JM. Structure of the inverted hexagonal (HII) phase, and non-lamellar phase transitions of lipids. Biochim Biophys Acta. 1990;1031:1–69.PubMedCrossRefGoogle Scholar
  14. 14.
    Seddon JM, Templer RH, Warrender NA, Huang Z, Cevc G, Marsh D. Phosphatidylcholine-fatty acid membranes: effects of headgroup hydration on the phase behaviour and structural parameters of the gel and inverse hexagonal (H||) phases. Biochim Biophys Acta. 1997;1327:131–47.PubMedCrossRefGoogle Scholar
  15. 15.
    Feigenson GW. Phase behavior of lipid mixtures. Nature Chem Biol. 2006;2:560–3.CrossRefGoogle Scholar
  16. 16.
    Zimmerberg J, Gawrisch K. The physical chemistry of biological membranes. Nature Chem Biol. 2006;2:564–7.CrossRefGoogle Scholar
  17. 17.
    Krepkiy D, Mihailescu M, Freites JA, Schow EV, Worcester DL, Gawrisch K, Tobias DJ, White SH, Swartz KJ. Structure and hydration of membranes embedded with voltage-sensing domains. Nature. 2009;462:473–9.PubMedCrossRefPubMedCentralGoogle Scholar
  18. 18.
    Phillips R, Ursell T, Wiggins P, Sens P. Emerging roles for lipids in shaping membrane-protein function. Nature. 2009;459:379–85.PubMedCrossRefPubMedCentralGoogle Scholar
  19. 19.
    Amazon JJ, Feigenson GW. Lattice simulations of phase morphology on lipid bilayers: renormalization, membrane shape, and electrostatic dipole interactions. Phys Rev E. 2014;89:022702.CrossRefGoogle Scholar
  20. 20.
    Feigenson GW. Pictures of the substructure of liquid-ordered domains. Biophys J. 2015;109:854–5.PubMedCrossRefPubMedCentralGoogle Scholar
  21. 21.
    Rheinstädter MC, Ollinger C, Fragneto G, Demmel F, Salditt T. Collective dynamics of lipid membranes studied by inelastic neutron scattering. Phys Rev Lett. 2004;93:108107.PubMedCrossRefGoogle Scholar
  22. 22.
    Brown MF, Chan SI. Bilayer membranes: deuterium and carbon-13 NMR. eMagRes. 2007:1–15.Google Scholar
  23. 23.
    Tyler AI, Clarke J, Seddon J, Law R. Solid state NMR of lipid model membranes. In: Owen DM, editor. Methods in membrane lipids. New York: Springer; 2015. p. 227–53.Google Scholar
  24. 24.
    Kaiser H-J, Lingwood D, Levental I, Sampaio JL, Kalvodova L, Rajendran L, Simons K. Order of lipid phases in model and plasma membranes. Proc Natl Acad Sci U S A. 2009;106:16645–50.PubMedCrossRefPubMedCentralGoogle Scholar
  25. 25.
    Orädd G, Shahedi V, Lindblom G. Effect of sterol structure on the bending rigidity of lipid membranes: a 2H NMR transverse relaxation study. Biochim Biophys Acta. 2009;1788:1762–71.PubMedCrossRefGoogle Scholar
  26. 26.
    Coskun U, Simons K. Cell membranes: the lipid perspective. Structure. 2011;19:1543–8.PubMedCrossRefGoogle Scholar
  27. 27.
    Kaye MD, Schmalzl K, Nibali VC, Tarek M, Rheinstädter MC. Ethanol enhances collective dynamics of lipid membranes. Phys Rev E. 2011;83(5 Pt 1):050907.CrossRefGoogle Scholar
  28. 28.
    Mallikarjunaiah KJ, Leftin A, Kinnun JJ, Justice MJ, Rogozea AL, Petrache HI, Brown MF. Solid-state 2H NMR shows equivalence of dehydration and osmotic pressures in lipid membrane deformation. Biophys J. 2011;100:98–107.PubMedCrossRefPubMedCentralGoogle Scholar
  29. 29.
    Leftin A, Xu X, Brown MF. Phospholipid bilayer membranes: deuterium and carbon-13 NMR spectroscopy. eMagRes. 2014;3:199–214.CrossRefGoogle Scholar
  30. 30.
    Kinnun JJ, Mallikarjunaiah KJ, Petrache HI, Brown MF. Elastic deformation and area per lipid of membranes: atomistic view from solid-state deuterium NMR spectroscopy. Biochim Biophys Acta. 2015;1848:246–59.PubMedCrossRefPubMedCentralGoogle Scholar
  31. 31.
    Shaghaghi M, Keyvanloo A, Huang ZH, Szoka FC, Thewalt JL. Constrained versus free cholesterol in DPPC membranes: a comparison of chain ordering ability using deuterium NMR. Langmuir. 2017;33:14405–13.PubMedCrossRefGoogle Scholar
  32. 32.
    Thewalt JL. Essential insights into lipid membrane organization from essential fatty acids. Biophys J. 2018;114:254–5.PubMedCrossRefGoogle Scholar
  33. 33.
    Molugu TR, Xu X, Lee S, Mallikarjunaiah KJ, Brown MF. Solid-state 2H NMR studies of water-mediated lipid membrane deformation. In: Webb GA, editor. Modern magnetic resonance. Cham: Springer; 2018. p. 1–27.Google Scholar
  34. 34.
    Soubias O, Teague WE Jr, Hines KG, Gawrisch K. Rhodopsin/lipid hydrophobic matching-rhodopsin oligomerization and function. Biophys J. 2015;108:1125–32.PubMedCrossRefPubMedCentralGoogle Scholar
  35. 35.
    Chawla U, Jiang YJ, Zheng W, Kuang LJ, Perera SMDC, Pitman MC, Brown MF, Liang HJ. A usual G-protein-coupled receptor in unusual membranes. Angew Chem Int Ed. 2016;55:588–92.CrossRefGoogle Scholar
  36. 36.
    Teague WE Jr, Soubias O, Petrache H, Fuller N, Hines KG, Rand RP, Gawrisch K. Elastic properties of polyunsaturated phosphatidylethanolamines influence rhodopsin function. Faraday Discuss. 2013;161:383–95.PubMedCrossRefPubMedCentralGoogle Scholar
  37. 37.
    Liang R, Li H, Swanson JMJ, Voth GA. Multiscale simulation reveals a multifaceted mechanism of proton permeation through the influenza A M2 proton channel. Proc Natl Acad Sci U S A. 2014;111:9396–401.PubMedCrossRefPubMedCentralGoogle Scholar
  38. 38.
    Soubias O, Teague WE, Hines KG, Gawrisch K. The role of membrane curvature elastic stress for function of rhodopsin-like G protein-coupled receptors. Biochimie. 2014;107:28–32.PubMedCrossRefPubMedCentralGoogle Scholar
  39. 39.
    Gondré-Lewis MC, Petrache HI, Wassif CA, Harries D, Parsegian A, Porter FD, Loh YP. Abnormal sterols in cholesterol-deficiency diseases cause secretory granule malformation and decreased membrane curvature. J Cell Sci. 2006;119:1876–85.PubMedCrossRefGoogle Scholar
  40. 40.
    Kumar GA, Jafurulla M, Chattopadhyay A. The membrane as the gatekeeper of infection: cholesterol in host–pathogen interaction. Chem Phys Lipids. 2016;199:179–85.PubMedCrossRefPubMedCentralGoogle Scholar
  41. 41.
    Eriksson JC, Henriksson U. Bridging-cluster model for hydrophobic attraction. Langmuir. 2007;23:10026–33.PubMedCrossRefPubMedCentralGoogle Scholar
  42. 42.
    Goñi FM, Alonso A, Bagatolli LA, Brown RE, Marsh D, Prieto M, Thewalt JL. Phase diagrams of lipid mixtures relevant to the study of membrane rafts. Biochim Biophys Acta. 2008;1781:665–84.PubMedCrossRefPubMedCentralGoogle Scholar
  43. 43.
    Escriba PV, Gonzalez-Ros JM, Goni FM, Kinnunen PKJ, Vigh L, Sanchez-Magraner L, Fernandez AM, Busquets X, Horvath I, Barcelo-Coblijn G. Membranes: a meeting point for lipids, proteins and therapies. J Cell Mol Med. 2008;12:829–75.PubMedCrossRefPubMedCentralGoogle Scholar
  44. 44.
    Armstrong CL, Barrett MA, Hiess A, Salditt T, Katsaras J, Shi A-C, Rheinstädter MC. Effect of cholesterol on the lateral nanoscale dynamics of fluid membranes. Eur Biophys J. 2012;41:901–13.PubMedCrossRefPubMedCentralGoogle Scholar
  45. 45.
    Armstrong CL, Marquardt D, Dies H, Kučerka N, Yamani Z, Harroun TA, Katsaras J, Shi A-C, Rheinstädter MC. The observation of highly ordered domains in membranes with cholesterol. Plos One. 2013;8:e66162.PubMedCrossRefPubMedCentralGoogle Scholar
  46. 46.
    Ackerman DG, Feigenson GW. Multiscale modeling of four-component lipid mixtures: domain composition, size, alignment, and properties of the phase interface. J Phys Chem B. 2015;119:4240–50.PubMedCrossRefPubMedCentralGoogle Scholar
  47. 47.
    Konyakhina TM, Feigenson GW. Phase diagram of a polyunsaturated lipid mixture: brain sphingomyelin/1-stearoyl-2-docosahexaenoyl-sn-glycero-3-phosphocholine/cholesterol. Biochim Biophys Acta. 2016;1858:153–61.PubMedCrossRefPubMedCentralGoogle Scholar
  48. 48.
    Epand RM. Lipid polymorphism and protein-lipid interactions. Biochim Biophys Acta. 1998;1376:353–68.PubMedCrossRefPubMedCentralGoogle Scholar
  49. 49.
    Epand RM. Cholesterol and the interaction of proteins with membrane domains. Prog Lipid Res. 2006;45:279–94.CrossRefGoogle Scholar
  50. 50.
    Scheidt HA, Meyer T, Nikolaus J, Baek DJ, Haralampiev I, Thomas L, Bittman R, Mueller P, Herrmann A, Huster D. Cholesterol’s aliphatic side chain modulates membrane properties. Angew Chem Int Ed. 2013;52:12848–51.CrossRefGoogle Scholar
  51. 51.
    Sodt AJ, Sandar ML, Gawrisch K, Pastor RW, Lyman E. The molecular structure of the liquid-ordered phase of lipid bilayers. J Am Chem Soc. 2014;136:725–32.PubMedCrossRefPubMedCentralGoogle Scholar
  52. 52.
    Levental I, Veatch SL. The continuing mystery of lipid rafts. J Mol Biol. 2016;428:4749–64.PubMedCrossRefPubMedCentralGoogle Scholar
  53. 53.
    Brown DA, London E. Functions of lipid rafts in biological membranes. Annu Rev Cell Dev Biol. 1998;14:111–36.PubMedCrossRefPubMedCentralGoogle Scholar
  54. 54.
    Golebiewska U, Scarlata S. The effect of membrane domains on the G protein-phospholipase Cβ signaling pathway. Crit Rev Biochem Mol Biol. 2010;45:97–105.PubMedCrossRefPubMedCentralGoogle Scholar
  55. 55.
    Simons K, Gerl MJ. Revitalizing membrane rafts: new tools and insights. Nat Rev Mol Cell Biol. 2010;11:688–99.PubMedCrossRefPubMedCentralGoogle Scholar
  56. 56.
    Simons K, Sampaio JL. Membrane organization and lipid rafts. Cold Spring Harb Perspect Biol. 2011;3:a004697.PubMedCrossRefPubMedCentralGoogle Scholar
  57. 57.
    Surma MA, Klose C, Simons K. Lipid-dependent protein sorting at the trans-Golgi network. Biochim Biophys Acta. 2012;1821:1059–67.PubMedCrossRefPubMedCentralGoogle Scholar
  58. 58.
    Klose C, Surma MA, Simons K. Organellar lipidomics – background and perspectives. Curr Opin Cell Biol. 2013;25:406–13.PubMedCrossRefPubMedCentralGoogle Scholar
  59. 59.
    Song Y, Kenworthy AK, Sanders CR. Cholesterol as a co-solvent and a ligand for membrane proteins. Prot Sci. 2014;23:1–22.CrossRefGoogle Scholar
  60. 60.
    Day CA, Kenworthy AK. Functions of cholera toxin B-subunit as a raft cross-linker. Essays Biochem. 2015;57:135–45.PubMedCrossRefPubMedCentralGoogle Scholar
  61. 61.
    Keller SL, McConnell HM. Stripe phases in lipid monolayers near a miscibility critical point. Phys Rev Lett. 1999;82:1602–5.CrossRefGoogle Scholar
  62. 62.
    Edidin M. The state of lipid rafts: from model membranes to cells. Annu Rev Biophys Biomol Struct. 2003;32:257–83.PubMedCrossRefPubMedCentralGoogle Scholar
  63. 63.
    Polozov IV, Gawrisch K. Characterization of the liquid-ordered state by proton MAS NMR. Biophys J. 2006;90:2051–61.PubMedCrossRefPubMedCentralGoogle Scholar
  64. 64.
    Veatch SL, Soubias O, Keller SL, Gawrisch K. Critical fluctuations in domain-forming lipid mixtures. Proc Natl Acad Sci U S A. 2007;104:17650–5.PubMedCrossRefPubMedCentralGoogle Scholar
  65. 65.
    Bartels T, Lankalapally RS, Bittman R, Beyer K, Brown MF. Raftlike mixtures of sphingomyelin and cholesterol investigated by solid-state 2H NMR spectroscopy. J Am Chem Soc. 2008;130:14521–32.PubMedCrossRefPubMedCentralGoogle Scholar
  66. 66.
    Korade Z, Kenworthy AK. Lipid rafts, cholesterol, and the brain. Neuropharmacology. 2008;55:1265–73.PubMedCrossRefPubMedCentralGoogle Scholar
  67. 67.
    Wassall SR, Stillwell W. Polyunsaturated fatty acid-cholesterol interactions: domain formation in membranes. Biochim Biophys Acta. 2009;1788:24–32.PubMedCrossRefPubMedCentralGoogle Scholar
  68. 68.
    Camley BA, Brown FLH. Dynamic simulations of multicomponent lipid membranes over long length and time scales. Phys Rev Lett. 2010;105:148102.PubMedCrossRefPubMedCentralGoogle Scholar
  69. 69.
    Lingwood D, Simons K. Lipid rafts as a membrane-organizing principle. Science. 2010;327:46–50.CrossRefGoogle Scholar
  70. 70.
    Leftin A, Job C, Beyer K, Brown MF. Solid-state 13C NMR reveals annealing of raft-like membranes containing cholesterol by the intrinsically disordered protein α-synuclein. J Mol Biol. 2013;425:2973–87.PubMedCrossRefPubMedCentralGoogle Scholar
  71. 71.
    Meinhardt S, Vink RLC, Schmid F. Monolayer curvature stabilizes nanoscale raft domains in mixed lipid bilayers. Proc Natl Acad Sci U S A. 2013;110:4476–81.PubMedCrossRefPubMedCentralGoogle Scholar
  72. 72.
    Quinn PJ. Structure of sphingomyelin bilayers and complexes with cholesterol forming membrane rafts. Langmuir. 2013;29:9447–56.PubMedCrossRefGoogle Scholar
  73. 73.
    Leftin A, Molugu TR, Job C, Beyer K, Brown MF. Area per lipid and cholesterol interactions in membranes by separated local-field 13C NMR spectroscopy. Biophys J. 2014;107:2274–86.PubMedCrossRefPubMedCentralGoogle Scholar
  74. 74.
    Ipsen JH, Karlström G, Mouritsen OG, Wennerström H, Zuckermann MJ. Phase equilibria in the phosphatidylcholine-cholesterol system. Biochim Biophys Acta. 1987;905:162–72.PubMedCrossRefGoogle Scholar
  75. 75.
    Vist MR, Davis JH. Phase-equilibria of cholesterol dipalmitoylphosphatidylcholine mixtures: 2H nuclear magnetic-resonance and differential scanning calorimetry. Biochemistry. 1990;29:451–64.PubMedCrossRefGoogle Scholar
  76. 76.
    Simons K, Ikonen E. How cells handle cholesterol. Science. 2000;290:1721–6.PubMedCrossRefPubMedCentralGoogle Scholar
  77. 77.
    Simons K, Toomre D. Lipid rafts and signal transduction. Nat Rev Mol Cell Biol. 2000;1:31–9.PubMedCrossRefPubMedCentralGoogle Scholar
  78. 78.
    Ge Y, Gao J, Jordan R, Naumann CA. Changes in cholesterol level alter integrin sequestration in raft-mimicking lipid mixtures. Biophys J. 2018;114:158–67.PubMedCrossRefPubMedCentralGoogle Scholar
  79. 79.
    Greenwood AI, Pan J, Mills TT, Nagle JF, Epand RM, Tristram-Nagle S. CRAC motif peptide of the HIV-1 gp41 protein thins SOPC membranes and interacts with cholesterol. Biochim Biophys Acta. 2008;1778:1120–30.PubMedCrossRefPubMedCentralGoogle Scholar
  80. 80.
    Baier CJ, Fantini J, Barrantes FJ. Disclosure of cholesterol recognition motifs in transmembrane domains of the human nicotinic acetylcholine receptor. Sci Rep. 2011;69:1–7.Google Scholar
  81. 81.
    Fantini J, Barrantes FJ. How cholesterol interacts with membrane proteins: an exploration of cholesterol-binding sites including CRAC, CARC, and tilted domains. Front Physiol. 2013;4:1–9.Google Scholar
  82. 82.
    Koufos E, Chang EH, Rasti ES, Krueger E, Brown AC. Use of a cholesterol recognition amino acid consensus peptide to inhibit binding of a bacterial toxin to cholesterol. Biochemistry. 2016;55:4787–97.PubMedCrossRefPubMedCentralGoogle Scholar
  83. 83.
    Jafurulla M, Tiwari S, Chattopadhyay A. Identification of cholesterol recognition amino acid consensus (CRAC) motif in G-protein coupled receptors. Biochim Biophys Res Commun. 2011;404:569–73.CrossRefGoogle Scholar
  84. 84.
    Vogel A, Tan K-T, Waldmann H, Feller SE, Brown MF, Huster D. Flexibility of Ras lipid modifications studied by 2H solid-state NMR and molecular dynamics simulations. Biophys J. 2007;93:2697–712.PubMedCrossRefPubMedCentralGoogle Scholar
  85. 85.
    Weise K, Huster D, Kapoor S, Triola G, Waldmann H, Winter R. Gibbs energy determinants of lipoprotein insertion into lipid membranes: the case study of Ras proteins. Faraday Discuss. 2013;161:549–61.PubMedCrossRefPubMedCentralGoogle Scholar
  86. 86.
    Hubbell WL, McConnell HM. Molecular motion in spin-labeled phospholipids and membranes. J Am Chem Soc. 1971;93:314–26.PubMedCrossRefPubMedCentralGoogle Scholar
  87. 87.
    Semer R, Gelerinter E. Spin label study of the effects of sterols on egg lecithin bilayers. Chem Phys Lipids. 1979;23:201–11.CrossRefGoogle Scholar
  88. 88.
    Delmelle M, Butler KW, Smith ICP. Saturation transfer electron-spin resonance spectroscopy as a probe of anisotropic motion in model membrane systems. Biochemistry. 1980;19:698–704.PubMedCrossRefPubMedCentralGoogle Scholar
  89. 89.
    Manukovsky N, Sanders E, Matalon E, Wolf SG, Goldfarb D. Membrane curvature and cholesterol effects on lipids packing and spin-labelled lipids conformational distributions. Mol Phys. 2013;111:2887–96.CrossRefGoogle Scholar
  90. 90.
    Williams JA, Wassall CD, Kemple MD, Wassall SR. An electron paramagnetic resonance method for measuring the affinity of a spin-labeled analog of cholesterol for phospholipids. J Membr Biol. 2013;246:689–96.PubMedCrossRefPubMedCentralGoogle Scholar
  91. 91.
    Cheng C-Y, Olijve LLC, Kausik R, Han S. Cholesterol enhances surface water diffusion of phospholipid bilayers. J Chem Phys. 2014;141:22D513.PubMedCrossRefPubMedCentralGoogle Scholar
  92. 92.
    Lai AL, Freed JH. HIV gp41 fusion peptide increases membrane ordering in a cholesterol-dependent fashion. Biophys J. 2014;106:172–81.PubMedCrossRefPubMedCentralGoogle Scholar
  93. 93.
    Stepien P, Polit A, Wisniewska-Becker A. Comparative EPR studies on lipid bilayer properties in nanodiscs and liposomes. Biochim Biophys Acta. 2015;1848:60–6.PubMedCrossRefPubMedCentralGoogle Scholar
  94. 94.
    Vitiello G, Falanga A, Alcides Petruk A, Merlino A, Fragneto G, Paduano L, Galdiero S, D'Errico G. Fusion of raft-like lipid bilayers operated by a membranotropic domain of the HSV-type I glycoprotein gH occurs through a cholesterol-dependent mechanism. Soft Matter. 2015;11:3003–16.PubMedCrossRefPubMedCentralGoogle Scholar
  95. 95.
    Lippert JL, Peticolas W l. Laser Raman investigation of effect of cholesterol on conformational changes in dipalmitoyl lecithin multilayers. Proc Natl Acad Sci U S A. 1971;68:1572–6.PubMedCrossRefPubMedCentralGoogle Scholar
  96. 96.
    Tantipolphan R, Rades T, Strachan CJ, Gordon KC, Medlicott NJ. Analysis of lecithin–cholesterol mixtures using Raman spectroscopy. J Pharm Biomed Anal. 2006;41:476–84.PubMedCrossRefPubMedCentralGoogle Scholar
  97. 97.
    Mendelsohn R. Laser-Raman spectroscopic study of egg lecithin and egg lecithin-cholesterol mixtures. Biochim Biophys Acta. 1972;290:15–21.PubMedCrossRefPubMedCentralGoogle Scholar
  98. 98.
    Umemura J, Cameron DG, Mantsch HH. A Fourier transform infrared spectroscopic study of the molecular interaction of cholesterol with 1,2-dipalmitoyl-sn-glycero-3-phosphocholine. Biochim Biophys Acta. 1980;602:32–44.PubMedCrossRefPubMedCentralGoogle Scholar
  99. 99.
    Gagoś M, Arczewska M. FTIR spectroscopic study of molecular organization of the antibiotic amphotericin B in aqueous solution and in DPPC lipid monolayers containing the sterols cholesterol and ergosterol. Eur Biophys J. 2012;41:663–73.PubMedCrossRefPubMedCentralGoogle Scholar
  100. 100.
    Xu XL, London E. The effect of sterol structure on membrane lipid domains reveals how cholesterol can induce lipid domain formation. Biochemistry. 2000;39:843–9.PubMedCrossRefPubMedCentralGoogle Scholar
  101. 101.
    Yasuda T, Matsumori N, Tsuchikawa H, Lonnfors M, Nyholm TKM, Slotte JP, Murata M. Formation of gel-like nanodomains in cholesterol-containing sphingomyelin or phosphatidylcholine binary membrane as examined by fluorescence lifetimes and 2H NMR spectra. Langmuir. 2015;31:13783–92.PubMedCrossRefGoogle Scholar
  102. 102.
    Iwasaki F, Suga K, Okamoto Y, Umakoshi H. Characterization of DDAB/cholesterol vesicles and its comparison with lipid/cholesterol vesicles. J Nanosci Nanotechnol. 2018;18:1989–94.PubMedCrossRefGoogle Scholar
  103. 103.
    Sparr E, Eriksson L, Bouwstra JA, Ekelund K. AFM study of lipid monolayers: III. Phase behavior of ceramides, cholesterol and fatty acids. Langmuir. 2001;17:164–72.CrossRefGoogle Scholar
  104. 104.
    Lawrence JC, Saslowsky DE, Edwardson JM, Henderson RM. Real-time analysis of the effects of cholesterol on lipid raft behavior using atomic force microscopy. Biophys J. 2003;84:1827–32.PubMedCrossRefPubMedCentralGoogle Scholar
  105. 105.
    Sacchi M, Balleza D, Vena G, Puia G, Facci P, Alessandrini A. Effect of neurosteroids on a model lipid bilayer including cholesterol: an atomic force microscopy study. Biochim Biophys Acta. 2015;1848:1258–67.PubMedCrossRefGoogle Scholar
  106. 106.
    Warschawski DE, Devaux PF. 1H-13C Polarization transfer in membranes: a tool for probing lipid dynamics and the effect of cholesterol. J Magn Reson. 2005;177:166–71.PubMedCrossRefGoogle Scholar
  107. 107.
    Holland GP, Alam TM. Multi-dimensional 1H-13C HETCOR and FSLG-HETCOR NMR study of sphingomyelin bilayers containing cholesterol in the gel and liquid crystalline states. J Magn Reson. 2006;181:316–26.PubMedCrossRefGoogle Scholar
  108. 108.
    Stockton GW, Polnaszek CF, Tulloch AP, Hasan F, Smith ICP. Molecular-motion and order in single-bilayer vesicles and multilamellar dispersions of egg lecithin and lecithin-cholesterol mixtures. A deuterium nuclear magnetic resonance study of specifically labeled lipids. Biochemistry. 1976;15:954–66.PubMedCrossRefGoogle Scholar
  109. 109.
    Brown MF. Anisotropic nuclear spin relaxation of cholesterol in phospholipid bilayers. Mol Phys. 1990;71:903–8.CrossRefGoogle Scholar
  110. 110.
    Weisz K, Gröbner G, Mayer C, Stohrer J, Kothe G. Deuteron nuclear magnetic resonance study of the dynamic organization of phospholipid/cholesterol bilayer membranes: molecular properties and viscoelastic behavior. Biochemistry. 1992;31:1100–12.PubMedCrossRefPubMedCentralGoogle Scholar
  111. 111.
    Martinez GV, Dykstra EM, Lope-Piedrafita S, Job C, Brown MF. NMR elastometry of fluid membranes in the mesoscopic regime. Phys Rev E. 2002;66:050902.CrossRefGoogle Scholar
  112. 112.
    Martinez GV, Dykstra EM, Lope-Piedrafita S, Brown MF. Lanosterol and cholesterol-induced variations in bilayer elasticity probed by 2H NMR relaxation. Langmuir. 2004;20:1043–6.PubMedCrossRefPubMedCentralGoogle Scholar
  113. 113.
    Bunge A, Mueller P, Stoeckl M, Herrmann A, Huster D. Characterization of the ternary mixture of sphingomyelin, POPC, and cholesterol: support for an inhomogeneous lipid distribution at high temperatures. Biophys J. 2008;94:2680–90.PubMedCrossRefPubMedCentralGoogle Scholar
  114. 114.
    Matsumori N, Yasuda T, Okazaki H, Suzuki T, Yamaguchi T, Tsuchikawa H, Doi M, Oishi T, Murata M. Comprehensive molecular motion capture for sphingomyelin by site-specific deuterium labeling. Biochemistry. 2012;51:8363–70.PubMedCrossRefPubMedCentralGoogle Scholar
  115. 115.
    Ferreira TM, Coreta-Gomes F, Ollila OHS, Moreno MJ, Vaz WLC, Topgaard D. Cholesterol and POPC segmental order parameters in lipid membranes: solid state 1H–13C NMR and MD simulation studies. Phys Chem Chem Phys. 2013;15:1976–89.PubMedCrossRefPubMedCentralGoogle Scholar
  116. 116.
    Shaghaghi M, Chen MT, Hsueh YW, Zuckermann MJ, Thewalt JL. Effect of sterol structure on the physical properties of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine membranes determined using 2H nuclear magnetic resonance. Langmuir. 2016;32:7654–63.PubMedCrossRefPubMedCentralGoogle Scholar
  117. 117.
    Vogel A, Scheidt HA, Baek DJ, Bittman R, Huster D. Structure and dynamics of the aliphatic cholesterol side chain in membranes as studied by 2H NMR spectroscopy and molecular dynamics simulation. Phys Chem Chem Phys. 2016;18:3730–8.PubMedCrossRefPubMedCentralGoogle Scholar
  118. 118.
    Molugu TR, Lee S, Brown MF. Concepts and methods of solid-state NMR spectroscopy applied to biomembranes. Chem Rev. 2017;117:12087–132.PubMedCrossRefPubMedCentralGoogle Scholar
  119. 119.
    Schmidt ML, Davis JH. Liquid disordered-liquid ordered phase coexistence in lipid/cholesterol mixtures: a deuterium 2D NMR exchange study. Langmuir. 2017;33:1881–90.PubMedCrossRefPubMedCentralGoogle Scholar
  120. 120.
    Ivankin A, Kuzmenko I, Gidalevitz D. Cholesterol-phospholipid interactions: new insights from surface X-ray scattering data. Phys Rev Lett. 2010;104:108101.PubMedCrossRefPubMedCentralGoogle Scholar
  121. 121.
    Pan J, Cheng X, Heberle FA, Mostofian B, Kučerka N, Drazba P, Katsaras J. Interactions between ether phospholipids and cholesterol as determined by scattering and molecular dynamics simulations. J Phys Chem B. 2012;116:14829–38.PubMedCrossRefPubMedCentralGoogle Scholar
  122. 122.
    Foglia F, Lawrence MJ, Demė B, Fragneto G, Barlow D. Neutron diffraction studies of the interaction between amphotericin B and lipid-sterol model membranes. Sci Rep. 2012;2:778.PubMedCrossRefPubMedCentralGoogle Scholar
  123. 123.
    Armstrong CL, Haeussler W, Seydel T, Katsaras J, Rheinstädter MC. Nanosecond lipid dynamics in membranes containing cholesterol. Soft Matter. 2014;10:2600–11.PubMedCrossRefGoogle Scholar
  124. 124.
    Toppozini L, Meinhardt S, Armstrong CL, Yamani Z, Kučerka N, Schmid F, Rheinstädter MC. Structure of cholesterol in lipid rafts. Phys Rev Lett. 2014;113:228101.PubMedCrossRefGoogle Scholar
  125. 125.
    McConnell H. Complexes in ternary cholesterol-phospholipid mixtures. Biophys J. 2005;88:L23–5.PubMedCrossRefPubMedCentralGoogle Scholar
  126. 126.
    Stanich CA, Honerkamp-Smith AR, Putzel GG, Warth CS, Lamprecht AK, Mandal P, Mann E, Hua T-AD, Keller SL. Coarsening dynamics of domains in lipid membranes. Biophys J. 2013;105:444–54.PubMedCrossRefPubMedCentralGoogle Scholar
  127. 127.
    Brown MF, Thurmond RL, Dodd SW, Otten D, Beyer K. Composite membrane deformation on the mesoscopic length scale. Phys Rev E. 2001;64:010901.CrossRefGoogle Scholar
  128. 128.
    Brown MF. Membrane structure and dynamics studied with NMR spectroscopy. In: Merz KM, Roux B, editors. Biological membranes: a molecular perspective from computation and experiment. Basel: Birkhäuser; 1996. p. 175–252.CrossRefGoogle Scholar
  129. 129.
    Leftin A, Brown MF. An NMR database for simulations of membrane dynamics. Biochim Biophys Acta. 2011;1808:818–39.PubMedCrossRefGoogle Scholar
  130. 130.
    Kinnun JJ, Leftin A, Brown MF. Solid-state NMR spectroscopy for the physical chemistry laboratory. J Chem Educ. 2013;90:123–8.CrossRefGoogle Scholar
  131. 131.
    Seelig J. Deuterium magnetic resonance: theory and application to lipid membranes. Q Rev Biophys. 1977;10:353–418.PubMedCrossRefGoogle Scholar
  132. 132.
    Seelig J, Seelig A. Lipid conformation in model membranes and biological membranes. Q Rev Biophys. 1980;13:19–61.PubMedCrossRefGoogle Scholar
  133. 133.
    Seelig J, Macdonald PM. Phospholipids and proteins in biological membranes. 2H NMR as a method to study structure, dynamics, and interactions. Acc Chem Res. 1987;20:221–8.CrossRefGoogle Scholar
  134. 134.
    Brown MF, Chan SI. Bilayer membranes: deuterium & carbon-13 NMR. In: Harris RK, Grant DM, editors. Encyclopedia of magnetic resonance. New York: Wiley; 1996. p. 871–85.Google Scholar
  135. 135.
    Brown MF, Lope-Piedrafita S, Martinez GV, Petrache HI. Solid-state deuterium NMR spectroscopy of membranes. In: Webb GA, editor. Modern magnetic resonance. Heidelberg: Springer; 2006. p. 245–56.Google Scholar
  136. 136.
    Xu X, Struts AV, Brown MF. Generalized model-free analysis of nuclear spin relaxation experiments. eMagRes. 2014;3:275–86.CrossRefGoogle Scholar
  137. 137.
    Rose ME. Elementary theory of angular momentum. New York: Wiley; 1957.CrossRefGoogle Scholar
  138. 138.
    Petrache HI, Dodd SW, Brown MF. Area per lipid and acyl length distributions in fluid phosphatidylcholines determined by 2H NMR spectroscopy. Biophys J. 2000;79:3172–92.PubMedCrossRefPubMedCentralGoogle Scholar
  139. 139.
    Thurmond RL, Dodd SW, Brown MF. Molecular areas of phospholipids as determined by 2H NMR spectroscopy: comparison of phosphatidylethanolamines and phosphatidylcholines. Biophys J. 1991;59:108–13.PubMedCrossRefPubMedCentralGoogle Scholar
  140. 140.
    Jansson M, Thurmond RL, Barry JA, Brown MF. Deuterium NMR study of intermolecular interactions in lamellar phases containing palmitoyllysophosphatidylcholine. J Phys Chem. 1992;96:9532–44.CrossRefGoogle Scholar
  141. 141.
    Nagle JF, Tristram-Nagle S. Structure of lipid bilayers. Biochim Biophys Acta. 2000;1469:159–95.PubMedCrossRefPubMedCentralGoogle Scholar
  142. 142.
    Pastor RW, Venable RM, Feller SE. Lipid bilayers, NMR relaxation, and computer simulations. Acc Chem Res. 2002;35:438–46.PubMedCrossRefGoogle Scholar
  143. 143.
    Huber T, Rajamoorthi K, Kurze VF, Beyer K, Brown MF. Structure of docosahexaenoic acid-containing phospholipid bilayers as studied by 2H NMR and molecular dynamics simulations. J Am Chem Soc. 2002;124:298–309.PubMedCrossRefPubMedCentralGoogle Scholar
  144. 144.
    Klauda JB, Venable RM, MacKerell AD Jr, Pastor RW. Considerations for lipid force field development. In: Feller SE, editor. Computational modeling of membrane bilayers; 2008. p. 1–48.Google Scholar
  145. 145.
    Klauda JB, Roberts MF, Redfield AG, Brooks BR, Pastor RW. Rotation of lipids in membranes: molecular dynamics simulation, 31P spin-lattice relaxation, and rigid-body dynamics. Biophys J. 2008;94:3074–83.PubMedCrossRefPubMedCentralGoogle Scholar
  146. 146.
    Klauda JB, Eldho NV, Gawrisch K, Brooks BR, Pastor RW. Collective and noncollective models of NMR relaxation in lipid vesicles and multilayers. J Phys Chem B. 2008;112:5924–9.PubMedCrossRefGoogle Scholar
  147. 147.
    Klauda JB, Venable RM, Freites JA, O'Connor JW, Tobias DJ, Mondragon-Ramirez C, Vorobyov I, MacKerell AD Jr, Pastor RW. Update of the CHARMM all-atom additive force field for lipids: validation on six lipid types. J Phys Chem B. 2010;114:7830–43.PubMedCrossRefPubMedCentralGoogle Scholar
  148. 148.
    Venable RM, Sodt AJ, Rogaski B, Rui H, Hatcher E, MacKerell AD Jr, Pastor RW, Klauda JB. CHARMM all-atom additive force field for sphingomyelin: elucidation of hydrogen bonding and of positive curvature. Biophys J. 2014;107:134–45.PubMedCrossRefPubMedCentralGoogle Scholar
  149. 149.
    Gruner SM. Stability of lyotropic phases with curved interfaces. J Phys Chem. 1989;93:7562–70.CrossRefGoogle Scholar
  150. 150.
    Gawrisch K. Tafazzin senses curvature. Nature Chem Biol. 2012;8:811–2.CrossRefGoogle Scholar
  151. 151.
    Brown MF, Seelig J. Influence of cholesterol on the polar region of phosphatidylcholine and phosphatidylethanolamine bilayers. Biochemistry. 1978;17:381–4.PubMedCrossRefGoogle Scholar
  152. 152.
    Oldfield E, Meadows M, Rice D, Jacobs R. Spectroscopic studies of specifically deuterium labeled membrane systems. Nuclear magnetic resonance investigation of effects of cholesterol in model systems. Biochemistry. 1978;17:2727–40.PubMedCrossRefGoogle Scholar
  153. 153.
    Trouard TP, Nevzorov AA, Alam TM, Job C, Zajicek J, Brown MF. Influence of cholesterol on dynamics of dimyristoylphosphatidylcholine as studied by deuterium NMR relaxation. J Chem Phys. 1999;110:8802–18.CrossRefGoogle Scholar
  154. 154.
    Salmon A, Dodd SW, Williams GD, Beach JM, Brown MF. Configurational statistics of acyl chains in polyunsaturated lipid bilayers from 2H NMR. J Am Chem Soc. 1987;109:2600–9.CrossRefGoogle Scholar
  155. 155.
    Wiedmann TS, Pates RD, Beach JM, Salmon A, Brown MF. Lipid-protein interactions mediate the photochemical function of rhodopsin. Biochemistry. 1988;27:6469–74.PubMedCrossRefGoogle Scholar
  156. 156.
    Petrache HI, Salmon A, Brown MF. Structural properties of docosahexaenoyl phospholipid bilayers investigated by solid-state 2H NMR spectroscopy. J Am Chem Soc. 2001;123:12611–22.PubMedCrossRefGoogle Scholar
  157. 157.
    Huber T, Botelho AV, Beyer K, Brown MF. Membrane model for the G-protein-coupled receptor rhodopsin: hydrophobic interface and dynamical structure. Biophys J. 2004;86:2078–100.PubMedCrossRefPubMedCentralGoogle Scholar
  158. 158.
    Shaikh SR, Kinnun JJ, Leng X, Williams JA, Wassall SR. How polyunsaturated fatty acids modify molecular organization in membranes: insight from NMR studies of model systems. Biochim Biophys Acta. 2015;1848:211–9.PubMedCrossRefGoogle Scholar
  159. 159.
    Zurzolo C, Simons K. Glycosylphosphatidylinositol-anchored proteins: membrane organization and transport. Biochim Biophys Acta. 2016;1858:632–9.PubMedCrossRefGoogle Scholar
  160. 160.
    Ahmed SN, Brown DA, London E. On the origin of sphingolipid/cholesterol-rich detergent-insoluble cell membranes: physiological concentrations of cholesterol and sphingolipid induce formation of a detergent-insoluble, liquid-ordered lipid phase in model membranes. Biochemistry. 1997;36:10944–53.PubMedCrossRefGoogle Scholar
  161. 161.
    Frisz JF, Lou KY, Klitzing HA, Hanafin WP, Lizunov V, Wilson RL, Carpenter KJ, Kim R, Hutcheon ID, Zimmerberg J, Weber PK, Kraft ML. Direct chemical evidence for sphingolipid domains in the plasma membranes of fibroblasts. Proc Natl Acad Sci U S A. 2013;110:E613–22.PubMedCrossRefPubMedCentralGoogle Scholar
  162. 162.
    Hsueh YW, Gilbert K, Trandum C, Zuckermann M, Thewalt J. The effect of ergosterol on dipalmitoylphosphatidylcholine bilayers: a deuterium NMR and calorimetric study. Biophys J. 2005;88:1799–808.PubMedCrossRefGoogle Scholar
  163. 163.
    Baoukina S, Rozmanov D, Tieleman DP. Composition fluctuations in lipid bilayers. Biophys J. 2017;113:2750–61.PubMedCrossRefPubMedCentralGoogle Scholar
  164. 164.
    Honerkamp-Smith AR, Veatch SL, Keller SL. An introduction to critical points for biophysicists; observations of compositional heterogeneity in lipid membranes. Biochim Biophys Acta. 2009;1788:53–63.PubMedCrossRefGoogle Scholar
  165. 165.
    Heberle FA, Marquardt D, Doktorova M, Geier B, Standaert RF, Heftberger P, Kollmitzer B, Nickels JD, Dick RA, Feigenson GW, Katsaras J, London E, Pabst G. Subnanometer structure of an asymmetric model membrane: interleaflet coupling influences domain properties. Langmuir. 2016;32:5195–200.PubMedCrossRefPubMedCentralGoogle Scholar
  166. 166.
    McConnell HM, Radhakrishnan A. Condensed complexes of cholesterol and phospholipids. Biochim Biophys Acta. 2003;1610:159–73.PubMedCrossRefGoogle Scholar
  167. 167.
    Ali MR, Cheng KH, Huang JY. Assess the nature of cholesterol-lipid interactions through the chemical potential of cholesterol in phosphatidylcholine bilayers. Proc Natl Acad Sci U S A. 2007;104:5372–7.PubMedCrossRefPubMedCentralGoogle Scholar
  168. 168.
    Pandit SA, Scott HL. Multiscale simulations of heterogeneous model membranes. Biochim Biophys Acta. 2009;1788:136–48.PubMedCrossRefGoogle Scholar
  169. 169.
    Longo GS, Schick M, Szleifer I. Stability and liquid-liquid phase separation in mixed saturated lipid bilayers. Biophys J. 2009;96:3977–86.PubMedCrossRefPubMedCentralGoogle Scholar
  170. 170.
    Rog T, Orlowski A, Llorente A, Skotland T, Sylvanne T, Kauhanen D, Ekroos K, Sandvig K, Vattulainen I. Interdigitation of long-chain sphingomyelin induces coupling of membrane leaflets in a cholesterol dependent manner. Biochim Biophys Acta. 2016;1858:281–8.PubMedCrossRefGoogle Scholar
  171. 171.
    Radhakrishnan A. Phase separations in binary and ternary cholesterol-phospholipid mixtures. Biophys J. 2010;98:L41–3.PubMedCrossRefPubMedCentralGoogle Scholar
  172. 172.
    Hsueh YW, Weng CJ, Chen MT, Thewalt J, Zuckermann M. Deuterium NMR study of the effect of ergosterol on POPE membranes. Biophys J. 2010;98:1209–17.PubMedCrossRefPubMedCentralGoogle Scholar
  173. 173.
    Miao L, Nielsen M, Thewalt J, Ipsen JH, Bloom M, Zuckermann MJ, Mouritsen OG. From lanosterol to cholesterol: structural evolution and differential effects on lipid bilayers. Biophys J. 2002;82:1429–44.PubMedCrossRefPubMedCentralGoogle Scholar
  174. 174.
    Greenwood AI, Tristram-Nagle S, Nagle JF. Partial molecular volumes of lipids and cholesterol. Chem Phys Lipids. 2006;143:1–10.PubMedCrossRefPubMedCentralGoogle Scholar
  175. 175.
    Keyvanloo A, Shaghaghi M, Zuckermann MJ, Thewalt JL. The phase behavior and organization of sphingomyelin/cholesterol membranes: a deuterium NMR study. Biophys J. 2018;114:1344–56.PubMedCrossRefPubMedCentralGoogle Scholar
  176. 176.
    Williams GD, Beach JM, Dodd SW, Brown MF. Dependence of deuterium spin-lattice relaxation rates of multilamellar phospholipid dispersions on orientational order. J Am Chem Soc. 1985;107:6868–73.CrossRefGoogle Scholar
  177. 177.
    Gross JD, Warschawski DE, Griffin RG. Dipolar recoupling in MAS NMR: a probe for segmental order in lipid bilayers. J Am Chem Soc. 1997;119:796–802.CrossRefGoogle Scholar
  178. 178.
    Gawrisch K, Eldho NV, Polozov IV. Novel NMR tools to study structure and dynamics of biomembranes. Chem Phys Lipids. 2002;116:135–51.PubMedCrossRefPubMedCentralGoogle Scholar
  179. 179.
    Brown MF, Deese AJ, Dratz EA. Proton, carbon-13, and phosphorus-31 NMR methods for the investigation of rhodopsin-lipid interactions in retinal rod outer segment membranes. Methods Enzymol. 1982;81:709–28.Google Scholar
  180. 180.
    Lee AG. How lipids affect the activities of integral membrane proteins. Biochim Biophys Acta. 2004;1666:62–87.PubMedCrossRefPubMedCentralGoogle Scholar
  181. 181.
    Ferreira TM, Medronho B, Martin RW, Topgaard D. Segmental order parameters in a nonionic surfactant lamellar phase studied with 1H-13C solid-state NMR. Phys Chem Chem Phys. 2008;10:6033–8.PubMedCrossRefPubMedCentralGoogle Scholar
  182. 182.
    Hong M, Schmidt-Rohr K, Pines A. NMR measurement of signs and magnitudes of C-Η dipolar couplings in lecithin. J Am Chem Soc. 1995;117:3310–1.CrossRefGoogle Scholar
  183. 183.
    Kobayashi M, Struts AV, Fujiwara T, Brown MF, Akutsu H. Fluid mechanical matching of H+-ATP synthase subunit c-ring with lipid membranes revealed by 2H solid-state NMR. Biophys J. 2008;94:4339–47.PubMedCrossRefPubMedCentralGoogle Scholar
  184. 184.
    Seelig J. General features of phospholipid conformation in membranes. Z Physiol Chem. 1978;359:1049–50.CrossRefGoogle Scholar
  185. 185.
    Brown MF. Theory of spin-lattice relaxation in lipid bilayers and biological membranes. 2H and 14N quadrupolar relaxation. J Chem Phys. 1982;77:1576–99.CrossRefGoogle Scholar
  186. 186.
    Trouard TP, Alam TM, Zajicek J, Brown MF. Angular anisotropy of 2H NMR spectral densities in phospholipid bilayers containing cholesterol. Chem Phys Lett. 1992;189:67–75.CrossRefGoogle Scholar
  187. 187.
    Barenholz Y, Thompson TE. Sphingomyelin: biophysical aspects. Chem Phys Lipids. 1999;102:29–34.PubMedCrossRefPubMedCentralGoogle Scholar
  188. 188.
    Yun-Wei C, Costa-Filho AJ, Freed JH. Dynamic molecular structure and phase diagram of DPPC-cholesterol binary mixtures: a 2D-ELDOR study. J Phys Chem B. 2007;111:11260–70.CrossRefGoogle Scholar
  189. 189.
    Smith AK, Freed JH. Determination of tie-line fields for coexisting lipid phases: an ESR study. J Phys Chem B. 2009;113:3957–71.PubMedCrossRefPubMedCentralGoogle Scholar
  190. 190.
    Tong J, Borbat PP, Freed JH, Shin Y-K. A scissors mechanism for stimulation of SNARE-mediated lipid mixing by cholesterol. Proc Natl Acad Sci U S A. 2009;106:5141–6.PubMedCrossRefPubMedCentralGoogle Scholar
  191. 191.
    Ipsen JH, Mouritsen OG, Bloom M. Relationships between lipid membrane area, hydrophobic thickness, and acyl-chain orientational order. The effects of cholesterol. Biophys J. 1990;57:405–12.PubMedCrossRefPubMedCentralGoogle Scholar
  192. 192.
    Chen Z, Rand RP. The influence of cholesterol on phospholipid membrane curvature and bending elasticity. Biophys J. 1997;73:267–76.PubMedCrossRefPubMedCentralGoogle Scholar
  193. 193.
    Filippov A, Orädd G, Lindblom G. The effect of cholesterol on the lateral diffusion of phospholipids in oriented bilayers. Biophys J. 2003;84:3079–86.PubMedCrossRefPubMedCentralGoogle Scholar
  194. 194.
    Ohvo-Rekilä H, Ramstedt B, Leppimäki P, Slotte JP. Cholesterol interactions with phospholipids in membranes. Prog Lipid Res. 2002;41:66–97.PubMedCrossRefPubMedCentralGoogle Scholar
  195. 195.
    Ramstedt B, Slotte JP. Sphingolipids and the formation of sterol-enriched ordered membrane domains. Biochim Biophys Acta. 2006;1758:1945–56.PubMedCrossRefPubMedCentralGoogle Scholar
  196. 196.
    Brown MF, Thurmond RL, Dodd SW, Otten D, Beyer K. Elastic deformation of membrane bilayers probed by deuterium NMR relaxation. J Am Chem Soc. 2002;124:8471–84.PubMedCrossRefGoogle Scholar
  197. 197.
    Brown MF. Unified picture for spin-lattice relaxation of lipid bilayers and biomembranes. J Chem Phys. 1984;80:2832–6.CrossRefGoogle Scholar
  198. 198.
    Klauda JB, Kučerka N, Brooks BR, Pastor RW, Nagle JF. Simulation-based methods for interpreting X-ray data from lipid bilayers. Biophys J. 2006;90:2796–807.PubMedCrossRefPubMedCentralGoogle Scholar
  199. 199.
    Brown MF. Theory of spin-lattice relaxation in lipid bilayers and biological membranes. Dipolar relaxation. J Chem Phys. 1984;80:2808–31.CrossRefGoogle Scholar
  200. 200.
    Nevzorov AA, Brown MF. Dynamics of lipid bilayers from comparative analysis of 2H and 13C nuclear magnetic resonance relaxation data as a function of frequency and temperature. J Chem Phys. 1997;107:10288–310.CrossRefGoogle Scholar
  201. 201.
    Nevzorov AA, Trouard TP, Brown MF. Lipid bilayer dynamics from simultaneous analysis of orientation and frequency dependence of deuterium spin-lattice and quadrupolar order relaxation. Phys Rev E. 1998;58:2259–81.CrossRefGoogle Scholar
  202. 202.
    Bloom M, Evans E. Observations of surface undulations on the mesoscopic length scale by NMR. In: Peliti L, editor. Biologically inspired physics. New York: Plenum; 1991. p. 137–47.CrossRefGoogle Scholar
  203. 203.
    Bloom M, Evans E, Mouritsen OG. Physical properties of the fluid lipid-bilayer component of cell membranes: a perspective. Q Rev Biophys. 1991;24:293–397.PubMedCrossRefPubMedCentralGoogle Scholar
  204. 204.
    Althoff G, Stauch O, Vilfan M, Frezzato D, Moro GJ, Hauser P, Schubert R, Kothe G. Transverse nuclear spin relaxation studies of viscoelastic properties of membrane vesicles. II. Experimental results. J Phys Chem B. 2002;106:5517–26.CrossRefGoogle Scholar
  205. 205.
    Althoff G, Frezzato D, Vilfan M, Stauch O, Schubert R, Vilfan I, Moro GJ, Kothe G. Transverse nuclear spin relaxation studies of viscoelastic properties of membrane vesicles. I. Theory. J Phys Chem B. 2002;106:5506–16.CrossRefGoogle Scholar
  206. 206.
    Brown MF, Ribeiro AA, Williams GD. New view of lipid bilayer dynamics from 2H and 13C NMR relaxation time measurements. Proc Natl Acad Sci U S A. 1983;80:4325–9.PubMedCrossRefPubMedCentralGoogle Scholar
  207. 207.
    Endress E, Heller H, Casalta H, Brown MF, Bayerl TM. Anisotropic motion and molecular dynamics of cholesterol, lanosterol, and ergosterol in lecithin bilayers studied by quasi-elastic neutron scattering. Biochemistry. 2002;41:13078–86.PubMedCrossRefPubMedCentralGoogle Scholar
  208. 208.
    Rog T, Pasenkiewicz-Gierula M, Vattulainen I, Karttunen M. What happens if cholesterol is made smoother: importance of methyl substituents in cholesterol ring structure on phosphatidylcholine-sterol interaction. Biophys J. 2007;92:3346–57.PubMedCrossRefPubMedCentralGoogle Scholar
  209. 209.
    Shahedi V, Orädd G, Lindblom G. Domain-formation in DOPC/SM bilayers studied by pfg-NMR: effect of sterol structure. Biophys J. 2006;91:2501–7.PubMedCrossRefPubMedCentralGoogle Scholar
  210. 210.
    Endress E, Bayerl S, Prechtel K, Maier C, Merkel R, Bayerl TM. The effect of cholesterol, lanosterol, and ergosterol on lecithin bilayer mechanical properties at molecular and microscopic dimensions: a solid-state NMR and micropipet study. Langmuir. 2002;18:3293–9.CrossRefGoogle Scholar
  211. 211.
    Yeagle PL, Martin RB, Lala AK, Lin H-K, Bloch K. Differential effects of cholesterol and lanosterol on artificial membranes. Proc Natl Acad Sci U S A. 1977;74:4924–6.PubMedCrossRefPubMedCentralGoogle Scholar
  212. 212.
    Bloch K. Sterol structure and membrane function. CRC Crit Rev Biochem. 1983;14:47–92.CrossRefGoogle Scholar
  213. 213.
    Yeagle PL. Lanosterol and cholesterol have different effects on phospholipid acyl chain ordering. Biochim Biophys Acta. 1985;815:33–6.PubMedCrossRefGoogle Scholar
  214. 214.
    Cheng K-H, Lepock JR, Hui SW, Yeagle PL. The role of cholesterol in the activity of reconstituted Ca-ATPase vesicles containing unsaturated phosphatidylethanolamine. J Biol Chem. 1986;261:5081–7.PubMedGoogle Scholar
  215. 215.
    Yeagle PL, Albert AD, Boesze-Battaglia K, Young J, Frye J. Cholesterol dynamics in membranes. Biophys J. 1990;57:413–24.PubMedCrossRefPubMedCentralGoogle Scholar
  216. 216.
    Henriksen J, Rowat AC, Brief E, Hsueh YW, Thewalt JL, Zuckermann MJ, Ipsen JH. Universal behavior of membranes with sterols. Biophys J. 2006;90:1639–49.PubMedCrossRefGoogle Scholar
  217. 217.
    Brief E, Kwak S, Cheng JTJ, Kitson N, Thewalt J, Lafleur M. Phase behavior of an equimolar mixture of N-palmitoyl-d 31-d-erythro-sphingosine, cholesterol, and palmitic acid, a mixture with optimized hydrophobic matching. Langmuir. 2009;25:7523–32.PubMedCrossRefGoogle Scholar
  218. 218.
    Huang JY, Feigenson GW. Monte Carlo simulation of lipid mixtures: finding phase separation. Biophys J. 1993;65:1788–94.PubMedCrossRefPubMedCentralGoogle Scholar
  219. 219.
    Hofsäß C, Lindahl E, Edholm O. Molecular dynamics simulations of phospholipid bilayers with cholesterol. Biophys J. 2003;84:2192–206.PubMedCrossRefPubMedCentralGoogle Scholar
  220. 220.
    Scheidt HA, Huster D. Structure and dynamics of the myristoyl lipid modification of Src peptides determined by 2H solid-state NMR spectroscopy. Biophys J. 2009;96:3663–72.PubMedCrossRefPubMedCentralGoogle Scholar
  221. 221.
    Penk A, Mueller M, Scheidt HA, Langosch D, Huster D. Structure and dynamics of the lipid modifications of a transmembrane α-helical peptide determined by 2H solid-state NMR spectroscopy. Biochim Biophys Acta. 2011;1808:784–91.PubMedCrossRefGoogle Scholar
  222. 222.
    Huster D. Solid-state NMR spectroscopy to study protein lipid interactions. Biochim Biophys Acta. 2014;1841:1146–60.PubMedCrossRefGoogle Scholar

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© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Department of Chemistry and BiochemistryUniversity of ArizonaTucsonUSA
  2. 2.Department of PhysicsUniversity of ArizonaTucsonUSA

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