Skip to main content
Log in

Rafts making and rafts braking: how plant flavonoids may control membrane heterogeneity

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

Plant flavonoids are not only known as powerful antioxidants, but also as cell metabolism regulators. It has been postulated that they are able to control cell signal pathways by targeting receptors on the cell surface or by intercalating the lipid bilayer of membranes. Some flavonoids can increase lipid viscosity and decrease the cooperativity of hydrocarbon chain melting, while others can considerably decrease the lipid melting temperature, thus providing additional freedom for lipid diffusion. Here we discuss the ability of flavonoids to influence phase transition and lateral segregation of lipids, responsible for the formation of membrane compartments known as lipid rafts. The thermodynamic parameters of the bilayer determined by lipid packing characteristics and by lateral segregation of the bilayer are expected to depend on the location of flavonoid molecules in the bilayer. Flavonoid molecules preferably located in the hydrophobic region of the bilayer can initiate formation of raft-like domains (raft-making effect), while the molecules located in the polar interface region of the bilayer can fluidize membranes (raft-breaking effect), or initiate formation of interdigitated or micellar structures. Accordingly, we expect that in cellular membranes flavonoids can influence the appearance and development of rafts or raft-like membrane domains and thus influence the lateral diffusion of lipid molecules. Because rafts participate in cellular signal transduction, endocytosis and transmembrane translocation of different compounds, flavonoids may control cell metabolism by modulating the bilayer state.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Jacobson K, Mouritsen OG, Anderson RG (2007) Lipid rafts: at a crossroad between cell biology and physics. Nat Cell Biol 9:7–14

    Article  PubMed  CAS  Google Scholar 

  2. Lichtenberg D, Goni F, Heerklotz H (2005) Detergent-resistant membranes should not be identified with membrane rafts. Trends Biochem Sci 30:430–436

    Article  PubMed  CAS  Google Scholar 

  3. Shaikh SR, Edidin MA (2006) Membranes are not just rafts. Chem Phys Lipids 144:1–3

    Article  PubMed  CAS  Google Scholar 

  4. Riethmuller J, Riehle A, Grassme H et al (2006) Membrane rafts in host-pathogen interactions. Biochim Biophys Acta 1758:2139–2147

    Article  PubMed  CAS  Google Scholar 

  5. Landry A, Xavier R (2006) Isolation and analysis of lipid rafts in cell-cell interactions. Methods Mol Biol 341:251–282

    PubMed  CAS  Google Scholar 

  6. Danielsen EM, Hansen GH (2006) Lipid raft organization and function in brush borders of epithelial cells. Mol Membr Biol 23:71–79

    Article  PubMed  CAS  Google Scholar 

  7. Kabouridis PS (2006) Lipid rafts in T cell receptor signalling. Mol Membr Biol 23:49–57

    Article  PubMed  CAS  Google Scholar 

  8. Zeyda M, Stulnig TM (2006) Lipid Rafts & Co.: an integrated model of membrane organization in T cell activation. Prog Lipid Res 45:187–202

    Article  PubMed  CAS  Google Scholar 

  9. Cordy JM, Hooper NM, Turner AJ (2006) The involvement of lipid rafts in Alzheimer’s disease. Mol Membr Biol 23:111–122

    Article  PubMed  CAS  Google Scholar 

  10. Murphy SC, Hiller NL, Harrison T et al (2006) Lipid rafts and malaria parasite infection of erythrocytes. Mol Membr Biol 23:81–88

    Article  PubMed  CAS  Google Scholar 

  11. Simons K, Vaz WL (2004) Model systems, lipid rafts, and cell membranes. Annu Rev Biophys Biomol Struct 33:269–295

    Article  PubMed  CAS  Google Scholar 

  12. Silvius JR (2005) Partitioning of membrane molecules between raft and non-raft domains: insights from model-membrane studies. Biochim Biophys Acta 1746:193–202

    Article  PubMed  CAS  Google Scholar 

  13. Szabo G, Dolganiuc A, Dai Q et al (2007) TLR4, ethanol, and lipid rafts: a new mechanism of ethanol action with implications for other receptor-mediated effects. J Immunol 178:1243–1249

    PubMed  CAS  Google Scholar 

  14. Siddiqui RA, Harvey KA, Zaloga GP et al (2007) Modulation of lipid rafts by Omega-3 fatty acids in inflammation and cancer: implications for use of lipids during nutrition support. Nutr Clin Pract 22:74–88

    Article  PubMed  Google Scholar 

  15. Saija A, Scalese M, Lanza M et al (1995) Flavonoids as antioxidant agents: importance of their interaction with biomembranes. Free Radic Biol Med 19:481–486

    Article  PubMed  CAS  Google Scholar 

  16. Ross JA, Kasum CM (2002) Dietary flavonoids: bioavailability, metabolic effects, and safety. Annu Rev Nutr 22:19–34

    Article  PubMed  CAS  Google Scholar 

  17. Williams RJ, Spencer JP, Rice-Evans C (2004) Flavonoids: antioxidants or signalling molecules? Free Radic Biol Med 36:838–849

    Article  PubMed  CAS  Google Scholar 

  18. Kroon P, Williamson G (2005) Polyphenols: dietary components with established benefits to health? J Sci Food Agric 85:1239–1240

    Article  CAS  Google Scholar 

  19. Dajas F, Rivera-Megret F, Blasina F et al (2003) Neuroprotection by flavonoids. Braz J Med Biol Res 36:1613–1620

    Article  PubMed  CAS  Google Scholar 

  20. Rietjens IM, Boersma MG, van der Woude H et al (2005) Flavonoids and alkenylbenzenes: mechanisms of mutagenic action and carcinogenic risk. Mutat Res 574:124–138

    PubMed  CAS  Google Scholar 

  21. Lopez-Lazaro M (2002) Flavonoids as anticancer agents: structure-activity relationship study. Curr Med Chem Anticancer Agents 2:691–714

    Article  PubMed  CAS  Google Scholar 

  22. Jovanovic SV, Steenken S, Tosic M et al (1994) Flavonoids as antioxidants. J Am Chem Soc 116:4846–4851

    Article  CAS  Google Scholar 

  23. Gamet-Payrastre L, Manenti S, Gratacap MP et al (1999) Flavonoids and the inhibition of PKC and PI3-kinase. Gen Pharmacol 32:279–286

    Article  PubMed  CAS  Google Scholar 

  24. Barzilai A, Rahamimoff H (1983) Inhibition of Ca2+-transport ATPase from synaptosomal vesicles by flavonoids. Biochim Biophys Acta 730:245–254

    Article  PubMed  CAS  Google Scholar 

  25. Bito T, Roy S, Sen CK et al (2002) Flavonoids differentially regulate IFN gamma-induced ICAM-1 expression in human keratinocytes: molecular mechanisms of action. FEBS Lett 520:145–152

    Article  PubMed  CAS  Google Scholar 

  26. Fujimura Y, Yamada K, Tachibana H (2005) A lipid raft-associated 67 kDa laminin receptor mediates suppressive effect of epigallocatechin-3-O-gallate on FcepsilonRI expression. Biochem Biophys Res Commun 336:674–681

    Article  PubMed  CAS  Google Scholar 

  27. Fujimura Y, Umeda D, Kiyohara Y et al (2006) The involvement of the 67 kDa laminin receptor-mediated modulation of cytoskeleton in the degranulation inhibition induced by epigallocatechin-3-O-gallate. Biochem Biophys Res Commun 348:524–531

    Article  PubMed  CAS  Google Scholar 

  28. Tachibana H, Fujimura Y, Yamada K (2004) Tea polyphenol epigallocatechin-3-gallate associates with plasma membrane lipid rafts: lipid rafts mediate anti-allergic action of the catechin. Biofactors 21:383–385

    PubMed  CAS  Google Scholar 

  29. Fujimura Y, Tachibana H, Kumai R et al (2004) A difference between epigallocatechin-3-gallate and epicatechin-3-gallate on anti-allergic effect is dependent on their distinct distribution to lipid rafts. Biofactors 21:133–135

    PubMed  CAS  Google Scholar 

  30. Fujimura Y, Tachibana H, Yamada K (2004) Lipid raft-associated catechin suppresses the FcepsilonRI expression by inhibiting phosphorylation of the extracellular signal-regulated kinase1/2. FEBS Lett 556:204–210

    Article  PubMed  CAS  Google Scholar 

  31. Hendrich AB (2006) Flavonoid-membrane interactions: possible consequences for biological effects of some polyphenolic compounds. Acta Pharmacol Sin 27:27–40

    Article  PubMed  CAS  Google Scholar 

  32. van Dijk C, Driessen AJ, Recourt K (2000) The uncoupling efficiency and affinity of flavonoids for vesicles. Biochem Pharmacol 60:1593–1600

    Article  PubMed  Google Scholar 

  33. Scheidt HA, Pampel A, Nissler L et al (2004) Investigation of the membrane localization and distribution of flavonoids by high-resolution magic angle spinning NMR spectroscopy. Biochim Biophys Acta 1663:97–107

    Article  PubMed  CAS  Google Scholar 

  34. Klymchenko AS, Duportail G, Demchenko AP et al (2004) Bimodal distribution and fluorescence response of environment-sensitive probes in lipid bilayers. Biophys J 86:2929–2941

    PubMed  CAS  Google Scholar 

  35. Sengupta B, Chaudhuri S, Banerjee A et al (2004) Characterization of serotonin in protein and membrane mimetic environments: a spectroscopic study. Chem Biodivers 1:868–877

    Article  PubMed  CAS  Google Scholar 

  36. Chaudhuri S, Banerjee A, Basu K et al (2007) Interaction of flavonoids with red blood cell membrane lipids and proteins: antioxidant and antihemolytic effects. Int J Biol Macromol 41:42–48

    Article  PubMed  CAS  Google Scholar 

  37. Tsuchiya H, Nagayama M, Tanaka T et al (2002) Membrane-rigidifying effects of anti-cancer dietary factors. Biofactors 16:45–56

    PubMed  CAS  Google Scholar 

  38. McConnell HM, Vrljic M (2003) Liquid-liquid immiscibility in membranes. Annu Rev Biophys Biomol Struct 32:469–492

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  40. Lairion F, Disalvo EA (2004) Effect of phloretin on the dipole potential of phosphatidylcholine, phosphatidylethanolamine, and phosphatidylglycerol monolayers. Langmuir 20:9151–9155

    Article  PubMed  CAS  Google Scholar 

  41. Taylor AM, Watts A (1998) Spin-label studies of lipid-protein interactions with reconstituted band 3, the human erythrocyte chloride-bicarbonate exchanger. Biochem Cell Biol 76:815–822

    Article  PubMed  CAS  Google Scholar 

  42. Sabra MC, Uitdehaag JC, Watts A (1998) General model for lipid-mediated two-dimensional array formation of membrane proteins: application to bacteriorhodopsin. Biophys J 75:1180–1188

    PubMed  CAS  Google Scholar 

  43. Franklin JC, Cafiso DS (1993) Internal electrostatic potentials in bilayers: measuring and controlling dipole potentials in lipid vesicles. Biophys J 65:289–299

    PubMed  CAS  Google Scholar 

  44. Gawrisch K, Ruston D, Zimmerberg J et al (1992) Membrane dipole potentials, hydration forces, and the ordering of water at membrane surfaces. Biophys J 61:1213–1223

    PubMed  CAS  Google Scholar 

  45. Bechinger B, Seelig J (1991) Interaction of electric dipoles with phospholipid head groups. A 2H and 31P NMR study of phloretin and phloretin analogues in phosphatidylcholine membranes. Biochemistry 30:3923–3929

    Article  PubMed  CAS  Google Scholar 

  46. Dill KA, Stigter D (1988) Lateral interactions among phosphatidylcholine and phosphatidylethanolamine head groups in phospholipid monolayers and bilayers. Biochemistry 27:3446–3453

    Article  PubMed  CAS  Google Scholar 

  47. Cseh R, Benz R (1999) Interaction of phloretin with lipid monolayers: relationship between structural changes and dipole potential change. Biophys J 77:1477–1488

    PubMed  CAS  Google Scholar 

  48. Cseh R, Hetzer M, Wolf K et al (2000) Interaction of phloretin with membranes: on the mode of action of phloretin at the water-lipid interface. Eur Biophys J 29:172–183

    Article  PubMed  CAS  Google Scholar 

  49. Andersen OS, Finkelstein A, Katz I et al (1976) Effect of phloretin on the permeability of thin lipid membranes. J Gen Physiol 67:749–771

    Article  PubMed  CAS  Google Scholar 

  50. Melnik E, Latorre R, Hall JE et al (1977) Phloretin-induced changes in ion transport across lipid bilayer membranes. J Gen Physiol 69:243–257

    Article  PubMed  CAS  Google Scholar 

  51. Auner BG, O’Neill MA, Valenta C et al (2005) Interaction of phloretin and 6-ketocholestanol with DPPC-liposomes as phospholipid model membranes. Int J Pharm 294:149–155

    Article  PubMed  CAS  Google Scholar 

  52. 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 57:329–336

    Article  PubMed  CAS  Google Scholar 

  53. Huang C (1990) Mixed-chain phospholipids and interdigitated bilayer systems. Klin Wochenschr 68:149–165

    Article  PubMed  CAS  Google Scholar 

  54. Lu JZ, Hao YH, Chen JW (2001) Effect of cholesterol on the formation of an interdigitated gel phase in lysophosphatidylcholine and phosphatidylcholine binary mixtures. J Biochem (Tokyo) 129:891–898

    CAS  Google Scholar 

  55. Bondar OP, Pivovarenko VG, Rowe ES (1998) Flavonols—new fluorescent membrane probes for studying the interdigitation of lipid bilayers. Biochim Biophys Acta 1369:119–130

    Article  PubMed  CAS  Google Scholar 

  56. Rietveld A, Simons K (1998) The differential miscibility of lipids as the basis for the formation of functional membrane rafts. Biochim Biophys Acta 1376:467–479

    PubMed  CAS  Google Scholar 

  57. Zhao D, Sonawane ND, Levin MH et al (2007) Comparative transport efficiencies of urea analogues through urea transporter UT-B. Biochim Biophys Acta 1768:1815–1821

    Article  PubMed  CAS  Google Scholar 

  58. Kaur AR, Kanwar U, Nath SS (2006) Characteristics of glucose transport across the microvillous membranes of human term placenta. Nutr Hosp 21:38–46

    Google Scholar 

  59. Olson ML, Kargacin ME, Honeyman TW et al (2006) Effects of phytoestrogens on sarcoplasmic/endoplasmic reticulum calcium ATPase 2a and Ca2+ uptake into cardiac sarcoplasmic reticulum. J Pharmacol Exp Ther 316:628–635

    Article  PubMed  CAS  Google Scholar 

  60. Peerce BE, Fleming RY, Clarke RD (2003) Inhibition of human intestinal brush border membrane vesicle Na+-dependent phosphate uptake by phosphophloretin derivatives. Biochem Biophys Res Commun 301:8–12

    Article  PubMed  CAS  Google Scholar 

  61. Jennings ML, Solomon AK (1976) Interaction between phloretin and the red blood cell membrane. J Gen Physiol 67:381–383

    Article  PubMed  CAS  Google Scholar 

  62. Pohl P, Rokitskaya TI, Pohl EE et al (1997) Permeation of phloretin across bilayer lipid membranes monitored by dipole potential and microelectrode measurements. Biochim Biophys Acta 1323:163–172

    Article  PubMed  CAS  Google Scholar 

  63. Verkman AS, Solomon AK (1982) A stepwise mechanism for the permeation of phloretin through a lipid bilayer. J Gen Physiol 80:557–581

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Yury S. Tarahovsky.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Tarahovsky, Y.S., Muzafarov, E.N. & Kim, Y.A. Rafts making and rafts braking: how plant flavonoids may control membrane heterogeneity. Mol Cell Biochem 314, 65–71 (2008). https://doi.org/10.1007/s11010-008-9766-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11010-008-9766-9

Keywords

Navigation