Skip to main content
PMC home page
Biophysical Journal logoLink to Biophysical Journal
. 1999 Apr;76(4):2090–2098. doi: 10.1016/S0006-3495(99)77365-0

Membrane fusion promoters and inhibitors have contrasting effects on lipid bilayer structure and undulations.

T J McIntosh 1, K G Kulkarni 1, S A Simon 1
PMCID: PMC1300182  PMID: 10096904

Abstract

It has been established that the fusion of both biological membranes and phospholipid bilayers can be modulated by altering their lipid composition (Chernomordik et al., 1995 .J. Membr. Biol. 146:3). In particular, when added exogenously between apposing membranes, monomyristoylphosphatidylcholine (MMPC) inhibits membrane fusion, whereas glycerol monoleate (GMO), oleic acid (OA), and arachidonic acid (AA) promote fusion. This present study uses x-ray diffraction to investigate the effects of MMPC, GMO, OA, and AA on the bending and stability of lipid bilayers when bilayers are forced together with applied osmotic pressure. The addition of 10 and 30 mol% MMPC to egg phosphatidylcholine (EPC) bilayers maintains the bilayer structure, even when the interbilayer fluid spacing is reduced to approximately 3 A, and increases the repulsive pressure between bilayers so that the fluid spacing in excess water increases by 5 and 15 A, respectively. Thus MMPC increases the undulation pressure, implying that the addition of MMPC promotes out-of-plane bending and decreases the adhesion energy between bilayers. In contrast, the addition of GMO has minor effects on the undulation pressure; 10 and 50 mol% GMO increase the fluid spacing of EPC in excess water by 0 and 2 A, respectively. However, x-ray diffraction indicates that, at small interbilayer separations, GMO, OA, or AA converts the bilayer to a structure containing hexagonally packed scattering units approximately 50 A in diameter. Thus GMO, OA, or AA destabilizes bilayer structure as apposing bilayers are brought into contact, which could contribute to their role in promoting membrane fusion.

Full Text

The Full Text of this article is available as a PDF (123.6 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Basáez G., Goñi F. M., Alonso A. Effect of single chain lipids on phospholipase C-promoted vesicle fusion. A test for the stalk hypothesis of membrane fusion. Biochemistry. 1998 Mar 17;37(11):3901–3908. doi: 10.1021/bi9728497. [DOI] [PubMed] [Google Scholar]
  2. Blaurock A. E., Worthington C. R. Treatment of low angle x-ray data from planar and concentric multilayered structures. Biophys J. 1966 May;6(3):305–312. doi: 10.1016/S0006-3495(66)86658-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Chernomordik L. V., Melikyan G. B., Chizmadzhev Y. A. Biomembrane fusion: a new concept derived from model studies using two interacting planar lipid bilayers. Biochim Biophys Acta. 1987 Oct 5;906(3):309–352. doi: 10.1016/0304-4157(87)90016-5. [DOI] [PubMed] [Google Scholar]
  4. Chernomordik L. V., Vogel S. S., Sokoloff A., Onaran H. O., Leikina E. A., Zimmerberg J. Lysolipids reversibly inhibit Ca(2+)-, GTP- and pH-dependent fusion of biological membranes. FEBS Lett. 1993 Feb 22;318(1):71–76. doi: 10.1016/0014-5793(93)81330-3. [DOI] [PubMed] [Google Scholar]
  5. Chernomordik L. V., Zimmerberg J. Bending membranes to the task: structural intermediates in bilayer fusion. Curr Opin Struct Biol. 1995 Aug;5(4):541–547. doi: 10.1016/0959-440x(95)80041-7. [DOI] [PubMed] [Google Scholar]
  6. Chernomordik L., Chanturiya A., Green J., Zimmerberg J. The hemifusion intermediate and its conversion to complete fusion: regulation by membrane composition. Biophys J. 1995 Sep;69(3):922–929. doi: 10.1016/S0006-3495(95)79966-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Chernomordik L., Leikina E., Cho M. S., Zimmerberg J. Control of baculovirus gp64-induced syncytium formation by membrane lipid composition. J Virol. 1995 May;69(5):3049–3058. doi: 10.1128/jvi.69.5.3049-3058.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Epand R. M. Diacylglycerols, lysolecithin, or hydrocarbons markedly alter the bilayer to hexagonal phase transition temperature of phosphatidylethanolamines. Biochemistry. 1985 Dec 3;24(25):7092–7095. doi: 10.1021/bi00346a011. [DOI] [PubMed] [Google Scholar]
  9. Epand R. M., Epand R. F., Ahmed N., Chen R. Promotion of hexagonal phase formation and lipid mixing by fatty acids with varying degrees of unsaturation. Chem Phys Lipids. 1991 Jan-Feb;57(1):75–80. doi: 10.1016/0009-3084(91)90051-c. [DOI] [PubMed] [Google Scholar]
  10. Evans E. A., Parsegian V. A. Thermal-mechanical fluctuations enhance repulsion between bimolecular layers. Proc Natl Acad Sci U S A. 1986 Oct;83(19):7132–7136. doi: 10.1073/pnas.83.19.7132. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Gawrisch K., Parsegian V. A., Hajduk D. A., Tate M. W., Graner S. M., Fuller N. L., Rand R. P. Energetics of a hexagonal-lamellar-hexagonal-phase transition sequence in dioleoylphosphatidylethanolamine membranes. Biochemistry. 1992 Mar 24;31(11):2856–2864. doi: 10.1021/bi00126a003. [DOI] [PubMed] [Google Scholar]
  12. Griffith O. H., Dehlinger P. J., Van S. P. Shape of the hydrophobic barrier of phospholipid bilayers (evidence for water penetration in biological membranes). J Membr Biol. 1974;15(2):159–192. doi: 10.1007/BF01870086. [DOI] [PubMed] [Google Scholar]
  13. Günther-Ausborn S., Praetor A., Stegmann T. Inhibition of influenza-induced membrane fusion by lysophosphatidylcholine. J Biol Chem. 1995 Dec 8;270(49):29279–29285. doi: 10.1074/jbc.270.49.29279. [DOI] [PubMed] [Google Scholar]
  14. Günther-Ausborn S., Stegmann T. How lysophosphatidylcholine inhibits cell-cell fusion mediated by the envelope glycoprotein of human immunodeficiency virus. Virology. 1997 Sep 1;235(2):201–208. doi: 10.1006/viro.1997.8699. [DOI] [PubMed] [Google Scholar]
  15. Herbette L., Marquardt J., Scarpa A., Blasie J. K. A direct analysis of lamellar x-ray diffraction from hydrated oriented multilayers of fully functional sarcoplasmic reticulum. Biophys J. 1977 Nov;20(2):245–272. doi: 10.1016/S0006-3495(77)85547-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Hirschi K. K., Minnich B. N., Moore L. K., Burt J. M. Oleic acid differentially affects gap junction-mediated communication in heart and vascular smooth muscle cells. Am J Physiol. 1993 Dec;265(6 Pt 1):C1517–C1526. doi: 10.1152/ajpcell.1993.265.6.C1517. [DOI] [PubMed] [Google Scholar]
  17. Hoekstra D. Membrane fusion of enveloped viruses: especially a matter of proteins. J Bioenerg Biomembr. 1990 Apr;22(2):121–155. doi: 10.1007/BF00762943. [DOI] [PubMed] [Google Scholar]
  18. Hope M. J., Cullis P. R. The role of nonbilayer lipid structures in the fusion of human erythrocytes induced by lipid fusogens. Biochim Biophys Acta. 1981 Jan 8;640(1):82–90. doi: 10.1016/0005-2736(81)90533-2. [DOI] [PubMed] [Google Scholar]
  19. Kozlov M. M., Leikin S. L., Chernomordik L. V., Markin V. S., Chizmadzhev Y. A. Stalk mechanism of vesicle fusion. Intermixing of aqueous contents. Eur Biophys J. 1989;17(3):121–129. doi: 10.1007/BF00254765. [DOI] [PubMed] [Google Scholar]
  20. LeNeveu D. M., Rand R. P. Measurement and modification of forces between lecithin bilayers. Biophys J. 1977 May;18(2):209–230. doi: 10.1016/S0006-3495(77)85608-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Markin V. S., Kozlov M. M., Borovjagin V. L. On the theory of membrane fusion. The stalk mechanism. Gen Physiol Biophys. 1984 Oct;3(5):361–377. [PubMed] [Google Scholar]
  22. Martin I., Dubois M. C., Saermark T., Epand R. M., Ruysschaert J. M. Lysophosphatidylcholine mediates the mode of insertion of the NH2-terminal SIV fusion peptide into the lipid bilayer. FEBS Lett. 1993 Nov 1;333(3):325–330. doi: 10.1016/0014-5793(93)80680-s. [DOI] [PubMed] [Google Scholar]
  23. Martin I., Ruysschaert J. M. Lysophosphatidylcholine inhibits vesicles fusion induced by the NH2-terminal extremity of SIV/HIV fusogenic proteins. Biochim Biophys Acta. 1995 Nov 22;1240(1):95–100. doi: 10.1016/0005-2736(95)00171-4. [DOI] [PubMed] [Google Scholar]
  24. McIntosh T. J., Advani S., Burton R. E., Zhelev D. V., Needham D., Simon S. A. Experimental tests for protrusion and undulation pressures in phospholipid bilayers. Biochemistry. 1995 Jul 11;34(27):8520–8532. doi: 10.1021/bi00027a002. [DOI] [PubMed] [Google Scholar]
  25. McIntosh T. J., Holloway P. W. Determination of the depth of bromine atoms in bilayers formed from bromolipid probes. Biochemistry. 1987 Mar 24;26(6):1783–1788. doi: 10.1021/bi00380a042. [DOI] [PubMed] [Google Scholar]
  26. McIntosh T. J., Magid A. D., Simon S. A. Cholesterol modifies the short-range repulsive interactions between phosphatidylcholine membranes. Biochemistry. 1989 Jan 10;28(1):17–25. doi: 10.1021/bi00427a004. [DOI] [PubMed] [Google Scholar]
  27. McIntosh T. J., Magid A. D., Simon S. A. Range of the solvation pressure between lipid membranes: dependence on the packing density of solvent molecules. Biochemistry. 1989 Sep 19;28(19):7904–7912. doi: 10.1021/bi00445a053. [DOI] [PubMed] [Google Scholar]
  28. McIntosh T. J., Magid A. D., Simon S. A. Steric repulsion between phosphatidylcholine bilayers. Biochemistry. 1987 Nov 17;26(23):7325–7332. doi: 10.1021/bi00397a020. [DOI] [PubMed] [Google Scholar]
  29. McIntosh T. J., Simon S. A. Hydration force and bilayer deformation: a reevaluation. Biochemistry. 1986 Jul 15;25(14):4058–4066. doi: 10.1021/bi00362a011. [DOI] [PubMed] [Google Scholar]
  30. McIntosh T. J., Simon S. A., Needham D., Huang C. H. Interbilayer interactions between sphingomyelin and sphingomyelin/cholesterol bilayers. Biochemistry. 1992 Feb 25;31(7):2020–2024. doi: 10.1021/bi00122a018. [DOI] [PubMed] [Google Scholar]
  31. Parsegian V. A., Fuller N., Rand R. P. Measured work of deformation and repulsion of lecithin bilayers. Proc Natl Acad Sci U S A. 1979 Jun;76(6):2750–2754. doi: 10.1073/pnas.76.6.2750. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Parsegian V. A., Rand R. P., Fuller N. L., Rau D. C. Osmotic stress for the direct measurement of intermolecular forces. Methods Enzymol. 1986;127:400–416. doi: 10.1016/0076-6879(86)27032-9. [DOI] [PubMed] [Google Scholar]
  33. Pearson R. H., Pascher I. The molecular structure of lecithin dihydrate. Nature. 1979 Oct 11;281(5731):499–501. doi: 10.1038/281499a0. [DOI] [PubMed] [Google Scholar]
  34. Razinkov V. I., Melikyan G. B., Epand R. M., Epand R. F., Cohen F. S. Effects of spontaneous bilayer curvature on influenza virus-mediated fusion pores. J Gen Physiol. 1998 Oct;112(4):409–422. doi: 10.1085/jgp.112.4.409. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Siegel D. P. Energetics of intermediates in membrane fusion: comparison of stalk and inverted micellar intermediate mechanisms. Biophys J. 1993 Nov;65(5):2124–2140. doi: 10.1016/S0006-3495(93)81256-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Siegel D. P., Epand R. M. The mechanism of lamellar-to-inverted hexagonal phase transitions in phosphatidylethanolamine: implications for membrane fusion mechanisms. Biophys J. 1997 Dec;73(6):3089–3111. doi: 10.1016/S0006-3495(97)78336-X. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Südhof T. C. The synaptic vesicle cycle: a cascade of protein-protein interactions. Nature. 1995 Jun 22;375(6533):645–653. doi: 10.1038/375645a0. [DOI] [PubMed] [Google Scholar]
  38. Tardieu A., Luzzati V., Reman F. C. Structure and polymorphism of the hydrocarbon chains of lipids: a study of lecithin-water phases. J Mol Biol. 1973 Apr 25;75(4):711–733. doi: 10.1016/0022-2836(73)90303-3. [DOI] [PubMed] [Google Scholar]
  39. Tilcock C. P., Fisher D. Interactions of glycerol monooleate and dimethylsulphoxide with phospholipids. A differential scanning calorimetry and 31P-NMR study. Biochim Biophys Acta. 1982 Mar 8;685(3):340–346. doi: 10.1016/0005-2736(82)90075-x. [DOI] [PubMed] [Google Scholar]
  40. Van Echteld C. J., De Kruijff B., Mandersloot J. G., De Gier J. Effects of lysophosphatidylcholines on phosphatidylcholine and phosphatidylcholine/cholesterol liposome systems as revealed by 31P-NMR, electron microscopy and permeability studies. Biochim Biophys Acta. 1981 Dec 7;649(2):211–220. doi: 10.1016/0005-2736(81)90408-9. [DOI] [PubMed] [Google Scholar]
  41. Vogel S. S., Leikina E. A., Chernomordik L. V. Lysophosphatidylcholine reversibly arrests exocytosis and viral fusion at a stage between triggering and membrane merger. J Biol Chem. 1993 Dec 5;268(34):25764–25768. [PubMed] [Google Scholar]
  42. Weber T., Zemelman B. V., McNew J. A., Westermann B., Gmachl M., Parlati F., Söllner T. H., Rothman J. E. SNAREpins: minimal machinery for membrane fusion. Cell. 1998 Mar 20;92(6):759–772. doi: 10.1016/s0092-8674(00)81404-x. [DOI] [PubMed] [Google Scholar]
  43. White J. M. Membrane fusion. Science. 1992 Nov 6;258(5084):917–924. doi: 10.1126/science.1439803. [DOI] [PubMed] [Google Scholar]
  44. Wiener M. C., White S. H. Fluid bilayer structure determination by the combined use of x-ray and neutron diffraction. II. "Composition-space" refinement method. Biophys J. 1991 Jan;59(1):174–185. doi: 10.1016/S0006-3495(91)82209-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Worcester D. L., Franks N. P. Structural analysis of hydrated egg lecithin and cholesterol bilayers. II. Neutrol diffraction. J Mol Biol. 1976 Jan 25;100(3):359–378. doi: 10.1016/s0022-2836(76)80068-x. [DOI] [PubMed] [Google Scholar]
  46. Yeagle P. L., Smith F. T., Young J. E., Flanagan T. D. Inhibition of membrane fusion by lysophosphatidylcholine. Biochemistry. 1994 Feb 22;33(7):1820–1827. doi: 10.1021/bi00173a027. [DOI] [PubMed] [Google Scholar]

Articles from Biophysical Journal are provided here courtesy of The Biophysical Society

RESOURCES