The Journal of Membrane Biology

, Volume 246, Issue 12, pp 985–991 | Cite as

Phloretin-Induced Reduction in Dipole Potential of Sterol-Containing Bilayers

  • Olga S. Ostroumova
  • Svetlana S. Efimova
  • Ludmila V. Schagina


The phloretin-induced reduction in the dipole potential of planar lipid bilayers containing cholesterol, ergosterol, stigmasterol, 7-dehydrocholesterol and 5α-androstan-3β-ol was investigated. It is shown that effects depend on the type and concentration of membrane sterol. It is supposed that the effectiveness of phloretin in reducing the dipole potential of the bilayers that contain cholesterol, ergosterol and 7-dehydrocholesterol correlates with the ordering and condensing effects. The role of the concentration-dependent ability of different sterols to promote lateral heterogeneity in membranes is also discussed.


Phloretin Membrane dipole potential Sterol Lipid bilayer 



We are grateful to Prof. Valery V. Malev for fruitful discussions. This work was partly supported by the Russian Foundation for Basic Research (Grants 12-04-00948, 12-04-31332, 12-04-33121), the Program “Molecular and Cell Biology” of the Russian Academy of Sciences, a Grant from the president of RF (MK-1813.2012.4) and Russian state contract 8119 (MES, FTP, SSEPIR).

Supplementary material

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Supplementary material 1 (TIFF 18248 kb)


  1. Aittoniemi J, Róg T, Niemelä P, Pasenkiewicz-Gierula M, Karttunen M, Vattulainen I (2006) Tilt: major factor in sterols’ ordering capability in membranes. J Phys Chem B 110:25562–25564CrossRefPubMedGoogle Scholar
  2. Andersen OS, Finkelstein A, Katz I, Cass A (1976) Effect of phloretin on the permeability of thin lipid membranes. J Gen Physiol 67:749–771CrossRefPubMedGoogle Scholar
  3. Auner BG, O’Neill MA, Valenta C, Hadgraft J (2005) Interaction of phloretin and 6-ketocholestanol with DPPC-liposomes as phospholipid model membranes. Int J Pharm 294:149–155CrossRefPubMedGoogle Scholar
  4. Bergelson LO, Gawrisch K, Feretti JA, Blumenthal R (1995) Domain organization in biological membranes. Mol Membr Biol 12:1–162CrossRefGoogle Scholar
  5. Berring EE, Borrenpohl K, Fliesler SJ, Serfis AB (2005) A comparison of the behavior of cholesterol and selected derivatives in mixed sterol-phospholipid Langmuir monolayers: a fluorescence microscopy study. Chem Phys Lipids 136:1–12CrossRefPubMedGoogle Scholar
  6. Bhattacharyya AK, Connor WE (1974) Beta-sitosterolemia and xanthomatosis: a newly described lipid storage disease in two sisters. J Clin Invest 53:1033–1043PubMedCentralCrossRefPubMedGoogle Scholar
  7. Cournia Z, Ullmann GM, Smith JC (2007) Differential effects of cholesterol, ergosterol and lanosterol on a dipalmitoyl phosphatidylcholine membrane: a molecular dynamics simulation study. J Phys Chem 111:1786–1801CrossRefGoogle Scholar
  8. Cowan MM (1999) Plant products as antimicrobial agents. Clin Microbiol Rev 12:564–582PubMedCentralPubMedGoogle Scholar
  9. Cseh R, Benz R (1998) The adsorption of phloretin to lipid monolayers and bilayers cannot be explained by Langmuir adsorption isotherms alone. Biophys J 74:1399–1408PubMedCentralCrossRefPubMedGoogle Scholar
  10. Cseh R, Hetzer M, Wolf K, Kraus J, Bringmann G, Benz R (2000) Interaction of phloretin with membranes: on the mode of action of phloretin at the water–lipid interface. Eur Biophys J 29:172–183CrossRefPubMedGoogle Scholar
  11. De Levie R, Rangarajan SK, Seelig PF, Andersen OS (1979) On the adsorption of phloretin onto a black lipid membrane. Biophys J 25:295–300PubMedCentralCrossRefPubMedGoogle Scholar
  12. Disalvo EA, Lairion F, Martini F, Almaleck H (2004) Water in biological membranes at interfaces: does it play a functional role? J Argent Chem Soc 92:1–22Google Scholar
  13. Edidin M (2003) The state of lipid rafts: from model membranes to cells. Annu Rev Biophys Biomol Struct 32:257–283CrossRefPubMedGoogle Scholar
  14. Efimova SS, Ostroumova OS (2012) Effect of dipole modifiers on the magnitude of the dipole potential of sterol-containing bilayers. Langmuir 28:9908–9914CrossRefPubMedGoogle Scholar
  15. Flewelling RF, Hubbell WL (1986) The membrane dipole potential in a total membrane potential model: applications to hydrophobic ion interactions with membranes. Biophys J 49:541–552PubMedCentralCrossRefPubMedGoogle Scholar
  16. Gao W, Chen L, Wu R, Yu Z, Quinn PJ (2008) Phase diagram of androsterol-dipalmitoylphosphatidylcholine mixtures dispersed in excess water. J Phys Chem B 112:8375–8382CrossRefPubMedGoogle Scholar
  17. Goñi FM, Alonso A, Bagatolli LA, Brown RE, Marsh D, Prieto M, Thewalt JL (2008) Phase diagrams of lipid mixtures relevant to the study of membrane rafts. Biochim Biophys Acta 1781:665–684PubMedCentralCrossRefPubMedGoogle Scholar
  18. Havsteen BH (2002) The biochemistry and medical significance of the flavonoids. Pharmacol Ther 96:67–202CrossRefPubMedGoogle Scholar
  19. Malkov DY, Sokolov VS (1996) Fluorescent styryl dyes of the RH series affect a potential drop on the membrane/solution boundary. Biochim Biophys Acta 1278:197–204CrossRefPubMedGoogle Scholar
  20. Maxfield FR (2002) Plasma membrane microdomains. Curr Opin Cell Biol 14:483–487CrossRefPubMedGoogle Scholar
  21. McMullen TPW, Lewis RNAH, McElhaney RN (2004) Cholesterol–phospholipid interactions, the liquid-ordered phase in model and biological membranes. Curr Opin Colloid Interface Sci 8:459–468CrossRefGoogle Scholar
  22. Middleton E, Kandaswami C, Theoharides TC (2000) The effects of plant flavonoids on mammalian cells: implications for inflammation, heart disease, and cancer. Pharmacol Rev 52:673–751PubMedGoogle Scholar
  23. Montal M, Muller P (1972) Formation of bimolecular membranes from lipid monolayers and study of their electrical properties. Proc Natl Acad Sci USA 65:3561–3566CrossRefGoogle Scholar
  24. Mouritsen OG, Jorgensen K (1994) Dynamical order and disorder in lipid bilayers. Chem Phys Lipids 73:3–26CrossRefPubMedGoogle Scholar
  25. Mouritsen OG, Jorgensen K (1997) Small-scale lipid membrane structure: simulation vs. experiment. Curr Opin Struct Biol 7:518–527CrossRefPubMedGoogle Scholar
  26. O’Shea P (2005) Physical landscapes in biological membranes: physico-chemical terrains for spatio-temporal control of biomolecular interactions and behaviour. Philos Trans R Soc A 363:575–588CrossRefGoogle Scholar
  27. O’Shea P, Somekh MG, Barnes WL (2008) Shedding light on life: visualizing nature’s complexity. Phys World 21:29–34CrossRefGoogle Scholar
  28. Ostroumova OS, Efimova SS, Schagina LV (2013) Changes in the dipole potential of phospholipid membranes induced by the adsorption of flavonoids (in Russian). Biophysics 58:474–480CrossRefGoogle Scholar
  29. Porter FD (2000) RSH/Smith-Lemli-Opitz syndrome: a multiple congenital anomaly/mental retardation syndrome due to an inborn error of cholesterol biosynthesis. Mol Genet Metab 71:163–174CrossRefPubMedGoogle Scholar
  30. Reyes J, Greco F, Motais R, Latorre R (1983) Phloretin and phloretin analogs: mode of action in planar lipid bilayers and monolayers. J Membr Biol 72:93–103CrossRefGoogle Scholar
  31. Róg T, Pasenkiewicz-Gierula M, Vattulainen I, Karttunen M (2009) Ordering effects of cholesterol and its analogues. Biochim Biophys Acta 1788:97–121CrossRefPubMedGoogle Scholar
  32. Sackmann E (1995) Biological membranes architecture and function. In: Lipowsky R, Sackmann E (eds) Structure and dynamics of membranes. Elsevier, Amsterdam, pp 1–64Google Scholar
  33. Serfis AB, Brancato S, Fliesler SJ (2001) Comparative behavior of sterols in phosphatidylcholine-sterol monolayer films. Biochim Biophys Acta 1511:341–348CrossRefPubMedGoogle Scholar
  34. Simon SA, McIntosh TJ, Magid AD, Needham D (1992) Modulation of the interbilayer hydration pressure by the addition of dipoles at the hydrocarbon/water interface. Biophys J 61:786–799PubMedCentralCrossRefPubMedGoogle Scholar
  35. Simons K, Ikonen E (1997) Functional rafts in cell membranes. Nature 387:569–572CrossRefPubMedGoogle Scholar
  36. Starke-Peterkovic T, Clarke RJ (2009) Effect of headgroup on the dipole potential of phospholipid vesicles. Eur Biophys J 39:103–110CrossRefPubMedGoogle Scholar
  37. Tarahovsky YS, Muzafarov EN, Kim YA (2008) Raft making and rafts braking: how plant flavonoids may control membrane heterogeneity. Mol Cell Biochem 314:65–71CrossRefPubMedGoogle Scholar
  38. Thewalt JL, Bloom M (1992) Phosphatidylcholine: cholesterol phase diagrams. Biophys J 63:1176–1181PubMedCentralCrossRefPubMedGoogle Scholar
  39. Tsybulskaya MV, Antonenko YN, Tropsch AE, Yaguzhinskii LS (1984) Iodine-containing hormones—dipole modifiers of phospholipid membranes [in Russian]. Biophysics 29:801–805Google Scholar
  40. Valenta C, Steininger A, Auner BG (2004) Phloretin and 6-ketocholestanol: membrane interactions studied by a phospholipid/polydiacetylene colorimetric assay and differential scanning calorimetry. Eur J Pharm Biopharm 57:329–336CrossRefPubMedGoogle Scholar
  41. Xu X, Bittman R, Duportail G, Heissler D, Vilcheze C, London E (2001) Effect of the structure of natural sterols and sphingolipids on the formation of ordered sphingolipid/sterol domains (rafts). Comparison of cholesterol to plant, fungal, and disease-associated sterols and comparison of sphingomyelin, cerebrosides, and ceramide. J Biol Chem 276:33540–33546CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Olga S. Ostroumova
    • 1
  • Svetlana S. Efimova
    • 1
  • Ludmila V. Schagina
    • 1
  1. 1.Institute of Cytology of the Russian Academy of SciencesSaint PetersburgRussia

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