Skip to main content
PMC home page
Biophysical Journal logoLink to Biophysical Journal
. 1999 Jan;76(1 Pt 1):291–313. doi: 10.1016/S0006-3495(99)77197-3

The modified stalk mechanism of lamellar/inverted phase transitions and its implications for membrane fusion.

D P Siegel 1
PMCID: PMC1302519  PMID: 9876142

Abstract

A model of the energetics of lipid assemblies (Siegel. 1993. Biophys. J. 65:2124-2140) is used to predict the relative free energy of intermediates in the transitions between lamellar (Lalpha) inverted hexagonal (HII), and inverted cubic (QII) phases. The model was previously used to generate the modified stalk theory of membrane fusion. The modified stalk theory proposes that the lowest energy structures to form between apposed membranes are the stalk and the transmonolayer contact (TMC), respectively. The first steps in the Lalpha/HII and Lalpha/QII phase transitions are also intermembrane events: bilayers of the Lalpha phase must interact to form new topologies during these transitions. Hence the intermediates in these phase transitions should be similar to the intermediates in the modified stalk mechanism of fusion. The calculations here show that stalks and TMCs can mediate transitions between the Lalpha, QII, and HII phases. These predictions are supported by studies of the mechanism of these transitions via time-resolved cryoelectron microscopy (. Biophys. J. 66:402-414; Siegel and Epand. 1997. Biophys. J. 73:3089-3111), whereas the predictions of previously proposed transition mechanisms are not. The model also predicts that QII phases should be thermodynamically stable in all thermotropic lipid systems. The profound hysteresis in Lalpha/QII transitions in some phospholipid systems may be due to lipid composition-dependent effects other than differences in lipid spontaneous curvature. The relevant composition-dependent properties are the Gaussian curvature modulus and the membrane rupture tension, which could change the stability of TMCs. TMC stability also influences the rate of membrane fusion of apposed bilayers, so these two properties may also affect the fusion rate in model membrane and biomembrane systems. One way proteins catalyze membrane fusion may be by making local changes in these lipid properties. Finally, although the model identifies stalks and TMCs as the lowest energy intermembrane intermediates in fusion and lamellar/inverted phase transitions, the stalk and TMC energies calculated by the present model are still large. This suggests that there are deficiencies in the current model for intermediates or intermediate energies. The possible nature of these deficiencies is discussed.

Full Text

The Full Text of this article is available as a PDF (246.3 KB).

Selected References

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

  1. Anderson D. M., Gruner S. M., Leibler S. Geometrical aspects of the frustration in the cubic phases of lyotropic liquid crystals. Proc Natl Acad Sci U S A. 1988 Aug;85(15):5364–5368. doi: 10.1073/pnas.85.15.5364. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. 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]
  3. Briggs J., Caffrey M. The temperature-composition phase diagram of monomyristolein in water: equilibrium and metastability aspects. Biophys J. 1994 Mar;66(3 Pt 1):573–587. doi: 10.1016/s0006-3495(94)80847-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Caffrey M. Kinetics and mechanism of the lamellar gel/lamellar liquid-crystal and lamellar/inverted hexagonal phase transition in phosphatidylethanolamine: a real-time X-ray diffraction study using synchrotron radiation. Biochemistry. 1985 Aug 27;24(18):4826–4844. doi: 10.1021/bi00339a017. [DOI] [PubMed] [Google Scholar]
  5. Caffrey M. Kinetics and mechanism of transitions involving the lamellar, cubic, inverted hexagonal, and fluid isotropic phases of hydrated monoacylglycerides monitored by time-resolved X-ray diffraction. Biochemistry. 1987 Oct 6;26(20):6349–6363. doi: 10.1021/bi00394a008. [DOI] [PubMed] [Google Scholar]
  6. Caffrey M., Magin R. L., Hummel B., Zhang J. Kinetics of the lamellar and hexagonal phase transitions in phosphatidylethanolamine. Time-resolved x-ray diffraction study using a microwave-induced temperature jump. Biophys J. 1990 Jul;58(1):21–29. doi: 10.1016/S0006-3495(90)82350-X. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Chen Z., Rand R. P. The influence of cholesterol on phospholipid membrane curvature and bending elasticity. Biophys J. 1997 Jul;73(1):267–276. doi: 10.1016/S0006-3495(97)78067-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. 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]
  9. 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]
  10. Chernomordik L., Kozlov M. M., Zimmerberg J. Lipids in biological membrane fusion. J Membr Biol. 1995 Jul;146(1):1–14. doi: 10.1007/BF00232676. [DOI] [PubMed] [Google Scholar]
  11. Chung H., Caffrey M. The curvature elastic-energy function of the lipid-water cubic mesophase. Nature. 1994 Mar 17;368(6468):224–226. doi: 10.1038/368224a0. [DOI] [PubMed] [Google Scholar]
  12. Chung H., Caffrey M. The neutral area surface of the cubic mesophase: location and properties. Biophys J. 1994 Feb;66(2 Pt 1):377–381. doi: 10.1016/s0006-3495(94)80787-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Colotto A., Epand R. M. Structural study of the relationship between the rate of membrane fusion and the ability of the fusion peptide of influenza virus to perturb bilayers. Biochemistry. 1997 Jun 24;36(25):7644–7651. doi: 10.1021/bi970382u. [DOI] [PubMed] [Google Scholar]
  14. Colotto A., Martin I., Ruysschaert J. M., Sen A., Hui S. W., Epand R. M. Structural study of the interaction between the SIV fusion peptide and model membranes. Biochemistry. 1996 Jan 23;35(3):980–989. doi: 10.1021/bi951991+. [DOI] [PubMed] [Google Scholar]
  15. Cullis P. R., van Dijck P. W., de Kruijff B., de Gier J. Effects of cholesterol on the properties of equimolar mixtures of synthetic phosphatidylethanolamine and phosphatidylcholine. A 31P NMR and differential scanning calorimetry study. Biochim Biophys Acta. 1978 Oct 19;513(1):21–30. doi: 10.1016/0005-2736(78)90108-6. [DOI] [PubMed] [Google Scholar]
  16. Ellens H., Bentz J., Szoka F. C. Fusion of phosphatidylethanolamine-containing liposomes and mechanism of the L alpha-HII phase transition. Biochemistry. 1986 Jul 15;25(14):4141–4147. doi: 10.1021/bi00362a023. [DOI] [PubMed] [Google Scholar]
  17. Ellens H., Siegel D. P., Alford D., Yeagle P. L., Boni L., Lis L. J., Quinn P. J., Bentz J. Membrane fusion and inverted phases. Biochemistry. 1989 May 2;28(9):3692–3703. doi: 10.1021/bi00435a011. [DOI] [PubMed] [Google Scholar]
  18. Epand R. M., Lemay C. T. Lipid concentration affects the kinetic stability of dielaidoylphosphatidylethanolamine bilayers. Chem Phys Lipids. 1993 Dec;66(3):181–187. doi: 10.1016/0009-3084(93)90003-l. [DOI] [PubMed] [Google Scholar]
  19. Evans E., Needham D. Giant vesicle bilayers composed of mixtures of lipids, cholesterol and polypeptides. Thermomechanical and (mutual) adherence properties. Faraday Discuss Chem Soc. 1986;(81):267–280. doi: 10.1039/dc9868100267. [DOI] [PubMed] [Google Scholar]
  20. Fournier JB. Nontopological saddle-splay and curvature instabilities from anisotropic membrane inclusions. Phys Rev Lett. 1996 Jun 3;76(23):4436–4439. doi: 10.1103/PhysRevLett.76.4436. [DOI] [PubMed] [Google Scholar]
  21. Frederik P. M., Burger K. N., Stuart M. C., Verkleij A. J. Lipid polymorphism as observed by cryo-electron microscopy. Biochim Biophys Acta. 1991 Feb 25;1062(2):133–141. doi: 10.1016/0005-2736(91)90384-k. [DOI] [PubMed] [Google Scholar]
  22. Gagné J., Stamatatos L., Diacovo T., Hui S. W., Yeagle P. L., Silvius J. R. Physical properties and surface interactions of bilayer membranes containing N-methylated phosphatidylethanolamines. Biochemistry. 1985 Jul 30;24(16):4400–4408. doi: 10.1021/bi00337a022. [DOI] [PubMed] [Google Scholar]
  23. Gruner S. M., Tate M. W., Kirk G. L., So P. T., Turner D. C., Keane D. T., Tilcock C. P., Cullis P. R. X-ray diffraction study of the polymorphic behavior of N-methylated dioleoylphosphatidylethanolamine. Biochemistry. 1988 Apr 19;27(8):2853–2866. doi: 10.1021/bi00408a029. [DOI] [PubMed] [Google Scholar]
  24. Helfrich W. Elastic properties of lipid bilayers: theory and possible experiments. Z Naturforsch C. 1973 Nov-Dec;28(11):693–703. doi: 10.1515/znc-1973-11-1209. [DOI] [PubMed] [Google Scholar]
  25. Hui S. W., Stewart T. P., Boni L. T. The nature of lipidic particles and their roles in polymorphic transitions. Chem Phys Lipids. 1983 Aug;33(2):113–126. doi: 10.1016/0009-3084(83)90015-4. [DOI] [PubMed] [Google Scholar]
  26. Hui S. W., Stewart T. P., Boni L. T., Yeagle P. L. Membrane fusion through point defects in bilayers. Science. 1981 May 22;212(4497):921–923. doi: 10.1126/science.7233185. [DOI] [PubMed] [Google Scholar]
  27. Keller S. L., Bezrukov S. M., Gruner S. M., Tate M. W., Vodyanoy I., Parsegian V. A. Probability of alamethicin conductance states varies with nonlamellar tendency of bilayer phospholipids. Biophys J. 1993 Jul;65(1):23–27. doi: 10.1016/S0006-3495(93)81040-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Keller S. L., Gruner S. M., Gawrisch K. Small concentrations of alamethicin induce a cubic phase in bulk phosphatidylethanolamine mixtures. Biochim Biophys Acta. 1996 Jan 31;1278(2):241–246. doi: 10.1016/0005-2736(95)00229-4. [DOI] [PubMed] [Google Scholar]
  29. 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]
  30. Kozlov M. M., Leikin S., Rand R. P. Bending, hydration and interstitial energies quantitatively account for the hexagonal-lamellar-hexagonal reentrant phase transition in dioleoylphosphatidylethanolamine. Biophys J. 1994 Oct;67(4):1603–1611. doi: 10.1016/S0006-3495(94)80633-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Laggner P., Kriechbaum M. Phospholipid phase transitions: kinetics and structural mechanisms. Chem Phys Lipids. 1991 Mar;57(2-3):121–145. doi: 10.1016/0009-3084(91)90072-j. [DOI] [PubMed] [Google Scholar]
  32. Leikin S. L., Kozlov M. M., Chernomordik L. V., Markin V. S., Chizmadzhev Y. A. Membrane fusion: overcoming of the hydration barrier and local restructuring. J Theor Biol. 1987 Dec 21;129(4):411–425. doi: 10.1016/s0022-5193(87)80021-8. [DOI] [PubMed] [Google Scholar]
  33. Leikin S., Kozlov M. M., Fuller N. L., Rand R. P. Measured effects of diacylglycerol on structural and elastic properties of phospholipid membranes. Biophys J. 1996 Nov;71(5):2623–2632. doi: 10.1016/S0006-3495(96)79454-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Leventis R., Fuller N., Rand R. P., Yeagle P. L., Sen A., Zuckermann M. J., Silvius J. R. Molecular organization and stability of hydrated dispersions of headgroup-modified phosphatidylethanolamine analogues. Biochemistry. 1991 Jul 23;30(29):7212–7219. doi: 10.1021/bi00243a024. [DOI] [PubMed] [Google Scholar]
  35. Lewis R. N., Mannock D. A., McElhaney R. N., Turner D. C., Gruner S. M. Effect of fatty acyl chain length and structure on the lamellar gel to liquid-crystalline and lamellar to reversed hexagonal phase transitions of aqueous phosphatidylethanolamine dispersions. Biochemistry. 1989 Jan 24;28(2):541–548. doi: 10.1021/bi00428a020. [DOI] [PubMed] [Google Scholar]
  36. Lewis R. N., McElhaney R. N., Harper P. E., Turner D. C., Gruner S. M. Studies of the thermotropic phase behavior of phosphatidylcholines containing 2-alkyl substituted fatty acyl chains: a new class of phosphatidylcholines forming inverted nonlamellar phases. Biophys J. 1994 Apr;66(4):1088–1103. doi: 10.1016/S0006-3495(94)80890-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Longo M. L., Waring A. J., Hammer D. A. Interaction of the influenza hemagglutinin fusion peptide with lipid bilayers: area expansion and permeation. Biophys J. 1997 Sep;73(3):1430–1439. doi: 10.1016/S0006-3495(97)78175-X. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Mannock D. A., Lewis R. N., McElhaney R. N., Akiyama M., Yamada H., Turner D. C., Gruner S. M. Effect of the chirality of the glycerol backbone on the bilayer and nonbilayer phase transitions in the diastereomers of di-dodecyl-beta-D-glucopyranosyl glycerol. Biophys J. 1992 Nov;63(5):1355–1368. doi: 10.1016/S0006-3495(92)81713-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Mannock D. A., McElhaney R. N., Harper P. E., Gruner S. M. Differential scanning calorimetry and X-ray diffraction studies of the thermotropic phase behavior of the diastereomeric di-tetradecyl-beta-D-galactosyl glycerols and their mixture. Biophys J. 1994 Mar;66(3 Pt 1):734–740. doi: 10.1016/s0006-3495(94)80849-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. 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]
  41. 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]
  42. McIntosh T. J., Simon S. A. Area per molecule and distribution of water in fully hydrated dilauroylphosphatidylethanolamine bilayers. Biochemistry. 1986 Aug 26;25(17):4948–4952. doi: 10.1021/bi00365a034. [DOI] [PubMed] [Google Scholar]
  43. Morein S., Strandberg E., Killian J. A., Persson S., Arvidson G., Koeppe R. E., 2nd, Lindblom G. Influence of membrane-spanning alpha-helical peptides on the phase behavior of the dioleoylphosphatidylcholine/water system. Biophys J. 1997 Dec;73(6):3078–3088. doi: 10.1016/S0006-3495(97)78335-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Nanavati C., Markin V. S., Oberhauser A. F., Fernandez J. M. The exocytotic fusion pore modeled as a lipidic pore. Biophys J. 1992 Oct;63(4):1118–1132. doi: 10.1016/S0006-3495(92)81679-X. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Rand R. P., Fuller N. L., Gruner S. M., Parsegian V. A. Membrane curvature, lipid segregation, and structural transitions for phospholipids under dual-solvent stress. Biochemistry. 1990 Jan 9;29(1):76–87. doi: 10.1021/bi00453a010. [DOI] [PubMed] [Google Scholar]
  46. Rand R. P., Fuller N., Parsegian V. A., Rau D. C. Variation in hydration forces between neutral phospholipid bilayers: evidence for hydration attraction. Biochemistry. 1988 Oct 4;27(20):7711–7722. doi: 10.1021/bi00420a021. [DOI] [PubMed] [Google Scholar]
  47. Rand R. P., Reese T. S., Miller R. G. Phospholipid bilayer deformations associated with interbilayer contact and fusion. Nature. 1981 Sep 17;293(5829):237–238. doi: 10.1038/293237a0. [DOI] [PubMed] [Google Scholar]
  48. Seddon J. M. Structure of the inverted hexagonal (HII) phase, and non-lamellar phase transitions of lipids. Biochim Biophys Acta. 1990 Feb 28;1031(1):1–69. doi: 10.1016/0304-4157(90)90002-t. [DOI] [PubMed] [Google Scholar]
  49. Shyamsunder E., Gruner S. M., Tate M. W., Turner D. C., So P. T., Tilcock C. P. Observation of inverted cubic phase in hydrated dioleoylphosphatidylethanolamine membranes. Biochemistry. 1988 Apr 5;27(7):2332–2336. doi: 10.1021/bi00407a014. [DOI] [PubMed] [Google Scholar]
  50. Siegel D. P., Banschbach J. L. Lamellar/inverted cubic (L alpha/QII) phase transition in N-methylated dioleoylphosphatidylethanolamine. Biochemistry. 1990 Jun 26;29(25):5975–5981. doi: 10.1021/bi00477a014. [DOI] [PubMed] [Google Scholar]
  51. Siegel D. P., Banschbach J. L. Lamellar/inverted cubic (L alpha/QII) phase transition in N-methylated dioleoylphosphatidylethanolamine. Biochemistry. 1990 Jun 26;29(25):5975–5981. doi: 10.1021/bi00477a014. [DOI] [PubMed] [Google Scholar]
  52. Siegel D. P., Banschbach J., Alford D., Ellens H., Lis L. J., Quinn P. J., Yeagle P. L., Bentz J. Physiological levels of diacylglycerols in phospholipid membranes induce membrane fusion and stabilize inverted phases. Biochemistry. 1989 May 2;28(9):3703–3709. doi: 10.1021/bi00435a012. [DOI] [PubMed] [Google Scholar]
  53. Siegel D. P., Burns J. L., Chestnut M. H., Talmon Y. Intermediates in membrane fusion and bilayer/nonbilayer phase transitions imaged by time-resolved cryo-transmission electron microscopy. Biophys J. 1989 Jul;56(1):161–169. doi: 10.1016/S0006-3495(89)82661-X. [DOI] [PMC free article] [PubMed] [Google Scholar]
  54. 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]
  55. 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]
  56. Siegel D. P., Green W. J., Talmon Y. The mechanism of lamellar-to-inverted hexagonal phase transitions: a study using temperature-jump cryo-electron microscopy. Biophys J. 1994 Feb;66(2 Pt 1):402–414. doi: 10.1016/s0006-3495(94)80790-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
  57. Siegel D. P. Inverted micellar intermediates and the transitions between lamellar, cubic, and inverted hexagonal amphiphile phases. III. Isotropic and inverted cubic state formation via intermediates in transitions between L alpha and HII phases. Chem Phys Lipids. 1986 Dec 31;42(4):279–301. doi: 10.1016/0009-3084(86)90087-3. [DOI] [PubMed] [Google Scholar]
  58. Siegel D. P. Inverted micellar intermediates and the transitions between lamellar, cubic, and inverted hexagonal lipid phases. I. Mechanism of the L alpha----HII phase transitions. Biophys J. 1986 Jun;49(6):1155–1170. doi: 10.1016/S0006-3495(86)83744-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
  59. Siegel D. P. Inverted micellar intermediates and the transitions between lamellar, cubic, and inverted hexagonal lipid phases. II. Implications for membrane-membrane interactions and membrane fusion. Biophys J. 1986 Jun;49(6):1171–1183. doi: 10.1016/S0006-3495(86)83745-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  60. Sjölund M., Lindblom G., Rilfors L., Arvidson G. Hydrophobic molecules in lecithin-water systems. I. Formation of reversed hexagonal phases at high and low water contents. Biophys J. 1987 Aug;52(2):145–153. doi: 10.1016/S0006-3495(87)83202-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  61. Tate M. W., Eikenberry E. F., Turner D. C., Shyamsunder E., Gruner S. M. Nonbilayer phases of membrane lipids. Chem Phys Lipids. 1991 Mar;57(2-3):147–164. doi: 10.1016/0009-3084(91)90073-k. [DOI] [PubMed] [Google Scholar]
  62. Tate M. W., Gruner S. M. Lipid polymorphism of mixtures of dioleoylphosphatidylethanolamine and saturated and monounsaturated phosphatidylcholines of various chain lengths. Biochemistry. 1987 Jan 13;26(1):231–236. doi: 10.1021/bi00375a031. [DOI] [PubMed] [Google Scholar]
  63. Tate M. W., Gruner S. M. Temperature dependence of the structural dimensions of the inverted hexagonal (HII) phase of phosphatidylethanolamine-containing membranes. Biochemistry. 1989 May 16;28(10):4245–4253. doi: 10.1021/bi00436a019. [DOI] [PubMed] [Google Scholar]
  64. Tate M. W., Shyamsunder E., Gruner S. M., D'Amico K. L. Kinetics of the lamellar-inverse hexagonal phase transition determined by time-resolved X-ray diffraction. Biochemistry. 1992 Feb 4;31(4):1081–1092. doi: 10.1021/bi00119a017. [DOI] [PubMed] [Google Scholar]
  65. Tenchov B., Koynova R., Rapp G. Accelerated formation of cubic phases in phosphatidylethanolamine dispersions. Biophys J. 1998 Aug;75(2):853–866. doi: 10.1016/S0006-3495(98)77574-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  66. Veiro J. A., Khalifah R. G., Rowe E. S. P-31 nuclear magnetic resonance studies of the appearance of an isotropic component in dielaidoylphosphatidylethanolamine. Biophys J. 1990 Mar;57(3):637–641. doi: 10.1016/S0006-3495(90)82581-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
  67. Verkleij A. J. Lipidic intramembranous particles. Biochim Biophys Acta. 1984 Jan 27;779(1):43–63. doi: 10.1016/0304-4157(84)90003-0. [DOI] [PubMed] [Google Scholar]
  68. Verkleij A. J., Mombers C., Gerritsen W. J., Leunissen-Bijvelt L., Cullis P. R. Fusion of phospholipid vesicles in association with the appearance of lipidic particles as visualized by freeze fracturing. Biochim Biophys Acta. 1979 Aug 7;555(2):358–361. doi: 10.1016/0005-2736(79)90175-5. [DOI] [PubMed] [Google Scholar]
  69. Verkleij A. J., Momvers C., Leunissen-Bijvelt J., Ververgaert P. H. Lipidic intramembranous particles. Nature. 1979 May 10;279(5709):162–163. doi: 10.1038/279162a0. [DOI] [PubMed] [Google Scholar]

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

RESOURCES