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Effects of Sterol Mole Fraction on Membrane Lateral Organization: Linking Fluorescence Signals to Sterol Superlattices

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Perspectives on Fluorescence

Part of the book series: Springer Series on Fluorescence ((SS FLUOR,volume 17))

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Abstract

Research highlights cited here illustrate some unconventional usage of fluorescent probes in biophysical studies on sterol superlattices in model membranes. The use of small sterol mole fraction increments over a wide range correctly delineates the global trend as well as the fine details of the effects of sterol content on membrane properties. An alternating variation of fluorescence signals and membrane properties with sterol content, with maxima or minima appeared at critical sterol mole fractions, was observed in many different membrane systems and can be explained by the sterol superlattice model. This model has been progressing over the last two decades. The current model links sterol superlattice formation with condensed complex formation, gives a deeper understanding of the liquid-ordered phase, and reveals two concentration-induced sharp phase transitions immediately below and above a critical sterol mole fraction for maximal superlattice formation. The density and size of membrane rafts isolated from model membranes as detergent resistant membrane fragments show characteristics typical for sterol superlattices, which suggests that membrane rafts and sterol superlattices are closely related. The concept of sterol superlattice formation can be used to optimize liposomal drug formulations and develop a method for a facile screening of lipid-soluble antioxidants for potency and toxicity.

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References

  1. Chong PLG, Capes S, Wong PT (1989) Effects of hydrostatic pressure on the location of PRODAN in lipid bilayers: a FT-IR study. Biochemistry 28:8358–8363

    Article  CAS  Google Scholar 

  2. Khan TK, Chong PLG (2000) Studies of archaebacterial bipolar tetraether liposomes by perylene fluorescence. Biophys J 78:1390–1399

    Article  CAS  Google Scholar 

  3. Schroeder F (1984) Fluorescent sterols: probe molecules of membrane structure and function. Prog Lipid Res 23:97–113

    Article  CAS  Google Scholar 

  4. Grechishnikova IV, Bergstrom F, Johansson LBA, Brown RE, Molotkovsky JG (1999) New fluorescent cholesterol analogs as membrane probes. Biochim Biophys Acta 1420:189–202

    Article  CAS  Google Scholar 

  5. Huang J, Buboltz JT, Feigenson GW (1999) Maximum solubility of cholesterol in phosphatidylcholine and phosphatidylethanolamine bilayers. Biochim Biophys Acta 1417:89–100

    Article  CAS  Google Scholar 

  6. Chong PLG (1994) Evidence for regular distribution of sterols in liquid crystalline phosphatidylcholine bilayers. Proc Natl Acad Sci U S A 91:10069–10073

    Article  CAS  Google Scholar 

  7. Somerharju P, Virtanen JA, Cheng KH, Hermansson M (2009) The superlattice model of lateral organization of membranes and its implications on membrane lipid homeostasis. Biochim Biophys Acta 1788:12–23

    Article  CAS  Google Scholar 

  8. Liu F, Sugar IP, Chong PLG (1997) Cholesterol and ergosterol superlattices in three-component liquid crystalline lipid bilayers as revealed by dehydroergosterol fluorescence. Biophys J 72:2243–2254

    Article  CAS  Google Scholar 

  9. Chong PLG, Olsher M (2004) Fluorescence studies of the existence and functional importance of regular distributions in liposomal membranes. Soft Mater 2:85–108

    Article  CAS  Google Scholar 

  10. Chong PLG, Zhu W, Venegas B (2009) On the lateral structure of model membranes containing cholesterol. Biochim Biophys Acta 1788:2–11

    Article  CAS  Google Scholar 

  11. Virtanen JA, Ruonala M, Vauhkonen M, Somerharju P (1995) Lateral organization of liquid-crystalline cholesterol-dimyristoylphosphatidylcholine bilayers: evidence for domains with hexagonal and centered rectangular cholesterol superlattices. Biochemistry 34:11568–11581

    Article  CAS  Google Scholar 

  12. Chong PLG, Liu F, Wang MM, Truong K, Sugar IP, Brown RE (1996) Fluorescence evidence for cholesterol regular distribution in phosphatidylcholine and in sphingomyelin lipid bilayers. J Fluoresc 6:221–230

    Article  CAS  Google Scholar 

  13. Venegas B, Sugar IP, Chong PLG (2007) Critical factors for detection of biphasic changes in membrane properties at specific sterol mole fractions for maximal superlattice formation. J Phys Chem B 111:5180–5192

    Article  CAS  Google Scholar 

  14. Cannon B, Heath G, Huang J, Somerharju P, Virtanen JA, Cheng KH (2003) Time-resolved fluorescence and Fourier transform infrared spectroscopic investigations of lateral packing defects and superlattice domains in compositionally uniform cholesterol/phosphatidylcholine bilayers. Biophys J 84:3777–3791

    Article  CAS  Google Scholar 

  15. Melzak KA, Melzak SA, Gizeli E, Toca-Herrera JL (2012) Cholesterol organization in phosphatidylcholine liposomes: a surface plasmon resonance study. Materials 5:2306–2325

    Article  CAS  Google Scholar 

  16. Huang J (2002) Exploration of molecular interactions in cholesterol superlattices: effect of multibody interactions. Biophys J 83:1014–1025

    Article  CAS  Google Scholar 

  17. Helrich CS, Schmucker JA, Woodbury DJ (2006) Evidence that nystatin channels form at the boundaries, not the interiors of lipid domains. Biophys J 91:1116–1127

    Article  CAS  Google Scholar 

  18. Wang MM, Olsher M, Sugar IP, Chong PLG (2004) Cholesterol superlattice modulates the activity of cholesterol oxidase in lipid membranes. Biochemistry 43:2159–2166

    Article  CAS  Google Scholar 

  19. Ali MR, Cheng KH, Huang J (2007) Assess the nature of cholesterol-lipid interactions through the chemical potential of cholesterol in phosphatidylcholine bilayers. Proc Natl Acad Sci U S A 104:5372–5377

    Article  CAS  Google Scholar 

  20. Fidorra M, Duelund L, Leidy C, Simonsen AC, Bagatolli LA (2006) Absence of fluid-ordered/fluid-disordered phase coexistence in ceramide/POPC mixtures containing cholesterol. Biophys J 90:4437–4451

    Article  CAS  Google Scholar 

  21. Chong PLG, Venegas B, Olsher M (2007) Fluorescence detection of signs of sterol superlattice formation in lipid membranes. Methods Mol Biol 400:159–170

    Article  CAS  Google Scholar 

  22. Virtanen JA, Somerharju P, Kinnunen PKJ (1988) Prediction of patterns for the regular distribution of soluted guest molecules in liquid crystalline phospholipid membranes. J Mol Electron 4:233–236

    Google Scholar 

  23. Parker A, Miles K, Cheng KH, Huang J (2004) Lateral distribution of cholesterol in dioleoylphosphatidylcholine lipid bilayers: cholesterol-phospholipid interactions at high cholesterol limit. Biophys J 86:1532–1544

    Article  CAS  Google Scholar 

  24. Sugar IP, Tang D, Chong PLG (1994) Monte Carlo simulation of lateral distribution of molecules in a two-component lipid membrane. J Phys Chem 98:7201–7210

    Article  CAS  Google Scholar 

  25. Tang D, Chong PLG (1992) E/M dips. Evidence for lipids regularly distributed into hexagonal super-lattices in pyrene-PC/DMPC binary mixtures at specific concentrations. Biophys J 63:903–910

    Article  CAS  Google Scholar 

  26. Somerharju PJ, Virtanen JA, Eklund KK, Vainio P, Kinnunen PKJ (1985) 1-Palmitoyl-2-pyrenedecanoyl glycerophospholipids as membrane probes: evidence for regular distribution in liquid-crystalline phosphatidylcholine bilayers. Biochemistry 24:2773–2781

    Article  CAS  Google Scholar 

  27. Wang MM, Sugar IP, Chong PLG (1998) Role of the sterol superlattice in the partitioning of the antifungal drug nystatin into lipid membranes. Biochemistry 37:11797–11805

    Article  CAS  Google Scholar 

  28. McConnell HM, Radhakrishnan A (2003) Condensed complexes of cholesterol and phospholipids. Biochim Biophys Acta 1610:159–173

    Article  CAS  Google Scholar 

  29. Sugar IP, Chong PLG (2012) A statistical mechanical model of cholesterol/phospholipid mixtures: linking condensed complexes, superlattices, and the phase diagram. J Am Chem Soc 134:1164–1171

    Article  CAS  Google Scholar 

  30. Sugar IP (2008) On the inner structure and topology of clusters in two-component lipid bilayers. Comparison of monomer and dimer Ising models. J Phys Chem B 112:11631–11642

    Article  CAS  Google Scholar 

  31. Ipsen JH, Karlstrom G, Mouritsen OG, Wennerstrom H, Zuckermann MJ (1987) Phase equilibria in the phosphatidylcholine-cholesterol system. Biochim Biophys Acta 905:162–172

    Article  CAS  Google Scholar 

  32. Huang TH, Lee CWB, Das Gupta SK, Blume A, Griffin RG (1993) A 13C and 2H nuclear magnetic resonance study of phosphatidylcholine/cholesterol interactions: characterization of liquid-gel phases. Biochemistry 32:13277–13287

    Article  CAS  Google Scholar 

  33. Virtanen JA, Somerharju P (1999) Cholesterol superlattice model is compatible with the calorimetric behavior of cholesterol/phosphatidylcholine bilayers. J Phys Chem B 103:10289–10293

    Article  CAS  Google Scholar 

  34. Sugar IP, Simon I, Chong PLG (2013) Series of concentration induced phase transitions in cholesterol/phosphatidylcholine mixtures. Biophys J 104:2448–2455

    Article  CAS  Google Scholar 

  35. Simons K, Ikonen E (1997) Functional rafts in cell membranes. Nature 387:569–572

    Article  CAS  Google Scholar 

  36. Xu X, London E (2000) The effect of sterol structure on membrane lipid domains reveals how cholesterol can induce lipid domain formation. Biochemistry 39:843–849

    Article  CAS  Google Scholar 

  37. Kusumi A, Koyama-Honda I, Suzuki K (2004) Molecular dynamics and interactions for creation of stimulation-induced stabilized rafts from small unstable steady-state rafts. Traffic 5:213–230

    Article  CAS  Google Scholar 

  38. Dietrich C, Yang B, Fujiwara T, Kusumi A, Jacobson K (2002) Relationship of lipid rafts to transient confinement zones detected by single particle tracking. Biophys J 82:274–284

    Article  CAS  Google Scholar 

  39. Yoon SI (2007) Effect of cholesterol content on lipid microdomains in model membranes and cells. PhD Thesis, Temple University School of Medicine

    Google Scholar 

  40. Xu W, Yoon SI, Huang P, Wang Y, Chen C, Chong PLG, Liu-Chen LY (2006) Localization of the kappa opioid receptor in lipid rafts. J Pharmacol Exp Ther 317:1295–1306

    Article  CAS  Google Scholar 

  41. Nallamothu R, Wood GC, Kiani MF, Moore BM, Horton FP, Thoma LA (2006) A targeted liposome delivery system for combretastatin A4: formulation optimization through drug loading and in vitro release studies. J Pharm Sci Technol 60:144–155

    CAS  Google Scholar 

  42. Venegas B, Zhu W, Haloupek NB, Lee J, Zellhart E, Sugar IP, Kiani M, Chong PLG (2012) Cholesterol superlattice modulates combretastatin A4 disodium phosphate (CA4P) release from liposomes and CA4P cytotoxicity on mammary cancer cells. Biophys J 102:2086–2094

    Article  CAS  Google Scholar 

  43. Olsher M, Chong PLG (2008) Sterol superlattice affects antioxidant potency and can be used to assess adverse effects of antioxidants. Anal Biochem 382:1–8

    Article  CAS  Google Scholar 

  44. Sesso HD (2006) Carotenoids and cardiovascular disease: what research gaps remain? Curr Opin Lipidol 17:11–16

    Article  CAS  Google Scholar 

  45. Chong PLG, Olsher M (2007) Fluorometric assay for detection of sterol oxidation in liposomal membranes. Methods Mol Biol 400:145–158

    Article  CAS  Google Scholar 

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Acknowledgment

I thank AHA, DOD, ACS, NSF, and ARO for supporting the superlattice project and all the students, postdoctoral fellows, and collaborators involved, with special thanks to István Sugár, Su-In Yoon, and Berenice Venegas for re-using their data in this chapter.

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Correspondence to Parkson Lee-Gau Chong .

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Chong, P.LG. (2016). Effects of Sterol Mole Fraction on Membrane Lateral Organization: Linking Fluorescence Signals to Sterol Superlattices. In: Jameson, D. (eds) Perspectives on Fluorescence. Springer Series on Fluorescence, vol 17. Springer, Cham. https://doi.org/10.1007/4243_2016_8

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