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PMID: 9876142 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

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

Biophysical journal ·Vol. 76 ·No. 1 Pt 1 ·1999-01-00 ·Pages 291-313

Siegel DP

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.

MeSH Terms
Biophysical Phenomena Biophysics Kinetics Lipid Bilayers/chemistry Membrane Fusion Membrane Lipids/chemistry Models, Biological Thermodynamics
Chemicals
Lipid Bilayers Membrane Lipids
Authors & Affiliations
1 authors, click to expand affiliations / ORCID
Siegel D P
Chemistry Department, The Ohio State University, Columbus, Ohio 43210 USA. dsiegel@chemistry.ohio-state.edu
References (68)
68 references, click to expand
  1. 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 PMID: 718888
  2. Experimental tests for protrusion and undulation pressures in phospholipid bilayers.
    Biochemistry. 1995 Jul 11;34(27):8520-32 PMID: 7612594
  3. 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):1155-70 PMID: 3719074
  4. 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):1171-83 PMID: 3719075
  5. Observation of inverted cubic phase in hydrated dioleoylphosphatidylethanolamine membranes.
    Biochemistry. 1988 Apr 5;27(7):2332-6 PMID: 3382626
  6. 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):1088-103 PMID: 8038381
  7. Lamellar/inverted cubic (L alpha/QII) phase transition in N-methylated dioleoylphosphatidylethanolamine.
    Biochemistry. 1990 Jun 26;29(25):5975-81 PMID: 2383567
  8. Variation in hydration forces between neutral phospholipid bilayers: evidence for hydration attraction.
    Biochemistry. 1988 Oct 4;27(20):7711-22 PMID: 3207702
  9. The nature of lipidic particles and their roles in polymorphic transitions.
    Chem Phys Lipids. 1983 Aug;33(2):113-26 PMID: 6627529
  10. Phospholipid bilayer deformations associated with interbilayer contact and fusion.
    Nature. 1981 Sep 17-23;293(5829):237-8 PMID: 7278983
  11. The mechanism of lamellar-to-inverted hexagonal phase transitions in phosphatidylethanolamine: implications for membrane fusion mechanisms.
    Biophys J. 1997 Dec;73(6):3089-111 PMID: 9414222
  12. Structure of the inverted hexagonal (HII) phase, and non-lamellar phase transitions of lipids.
    Biochim Biophys Acta. 1990 Feb 28;1031(1):1-69 PMID: 2407291
  13. Hydrophobic molecules in lecithin-water systems. I. Formation of reversed hexagonal phases at high and low water contents.
    Biophys J. 1987 Aug;52(2):145-53 PMID: 2822159
  14. Intermediates in membrane fusion and bilayer/nonbilayer phase transitions imaged by time-resolved cryo-transmission electron microscopy.
    Biophys J. 1989 Jul;56(1):161-9 PMID: 2752086
  15. X-ray diffraction study of the polymorphic behavior of N-methylated dioleoylphosphatidylethanolamine.
    Biochemistry. 1988 Apr 19;27(8):2853-66 PMID: 3401452
  16. 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):21-9 PMID: 2383633
  17. Membrane fusion through point defects in bilayers.
    Science. 1981 May 22;212(4497):921-3 PMID: 7233185
  18. Physical properties and surface interactions of bilayer membranes containing N-methylated phosphatidylethanolamines.
    Biochemistry. 1985 Jul 30;24(16):4400-8 PMID: 4052405
  19. Phospholipid phase transitions: kinetics and structural mechanisms.
    Chem Phys Lipids. 1991 Mar;57(2-3):121-45 PMID: 2054900
  20. Measured effects of diacylglycerol on structural and elastic properties of phospholipid membranes.
    Biophys J. 1996 Nov;71(5):2623-32 PMID: 8913600
  21. 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):734-40 PMID: 8011905
  22. Nonbilayer phases of membrane lipids.
    Chem Phys Lipids. 1991 Mar;57(2-3):147-64 PMID: 2054901
  23. The curvature elastic-energy function of the lipid-water cubic mesophase.
    Nature. 1994 Mar 17;368(6468):224-6 PMID: 8145820
  24. Membrane fusion and inverted phases.
    Biochemistry. 1989 May 2;28(9):3692-703 PMID: 2751990
  25. Bending membranes to the task: structural intermediates in bilayer fusion.
    Curr Opin Struct Biol. 1995 Aug;5(4):541-7 PMID: 8528771
  26. Area per molecule and distribution of water in fully hydrated dilauroylphosphatidylethanolamine bilayers.
    Biochemistry. 1986 Aug 26;25(17):4948-52 PMID: 3768325
  27. Kinetics of the lamellar-inverse hexagonal phase transition determined by time-resolved X-ray diffraction.
    Biochemistry. 1992 Feb 4;31(4):1081-92 PMID: 1734957
  28. Lipid concentration affects the kinetic stability of dielaidoylphosphatidylethanolamine bilayers.
    Chem Phys Lipids. 1993 Dec;66(3):181-7 PMID: 8111934
  29. 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):358-61 PMID: 573139
  30. The temperature-composition phase diagram of monomyristolein in water: equilibrium and metastability aspects.
    Biophys J. 1994 Mar;66(3 Pt 1):573-87 PMID: 8011891
  31. Influence of membrane-spanning alpha-helical peptides on the phase behavior of the dioleoylphosphatidylcholine/water system.
    Biophys J. 1997 Dec;73(6):3078-88 PMID: 9414221
  32. 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):1355-68 PMID: 1477284
  33. 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 PMID: 3829210
  34. Bending, hydration and interstitial energies quantitatively account for the hexagonal-lamellar-hexagonal reentrant phase transition in dioleoylphosphatidylethanolamine.
    Biophys J. 1994 Oct;67(4):1603-11 PMID: 7819492
  35. Lipids in biological membrane fusion.
    J Membr Biol. 1995 Jul;146(1):1-14 PMID: 7563032
  36. Geometrical aspects of the frustration in the cubic phases of lyotropic liquid crystals.
    Proc Natl Acad Sci U S A. 1988 Aug;85(15):5364-8 PMID: 3399497
  37. Physiological levels of diacylglycerols in phospholipid membranes induce membrane fusion and stabilize inverted phases.
    Biochemistry. 1989 May 2;28(9):3703-9 PMID: 2751991
  38. P-31 nuclear magnetic resonance studies of the appearance of an isotropic component in dielaidoylphosphatidylethanolamine.
    Biophys J. 1990 Mar;57(3):637-41 PMID: 2306507
  39. Structural study of the interaction between the SIV fusion peptide and model membranes.
    Biochemistry. 1996 Jan 23;35(3):980-9 PMID: 8547281
  40. Nontopological saddle-splay and curvature instabilities from anisotropic membrane inclusions.
    Phys Rev Lett. 1996 Jun 3;76(23):4436-4439 PMID: 10061289
  41. 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):541-8 PMID: 2713331
  42. Membrane fusion: overcoming of the hydration barrier and local restructuring.
    J Theor Biol. 1987 Dec 21;129(4):411-25 PMID: 3455469
  43. Lipidic intramembranous particles.
    Biochim Biophys Acta. 1984 Jan 27;779(1):43-63 PMID: 6362726
  44. 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):6349-63 PMID: 3427010
  45. On the theory of membrane fusion. The stalk mechanism.
    Gen Physiol Biophys. 1984 Oct;3(5):361-77 PMID: 6510702
  46. Biomembrane fusion: a new concept derived from model studies using two interacting planar lipid bilayers.
    Biochim Biophys Acta. 1987 Oct 5;906(3):309-52 PMID: 3307918
  47. Stalk mechanism of vesicle fusion. Intermixing of aqueous contents.
    Eur Biophys J. 1989;17(3):121-9 PMID: 2792021
  48. Lipid polymorphism as observed by cryo-electron microscopy.
    Biochim Biophys Acta. 1991 Feb 25;1062(2):133-41 PMID: 2004103
  49. Energetics of intermediates in membrane fusion: comparison of stalk and inverted micellar intermediate mechanisms.
    Biophys J. 1993 Nov;65(5):2124-40 PMID: 8298039
  50. Membrane curvature, lipid segregation, and structural transitions for phospholipids under dual-solvent stress.
    Biochemistry. 1990 Jan 9;29(1):76-87 PMID: 2322550
  51. Fusion of phosphatidylethanolamine-containing liposomes and mechanism of the L alpha-HII phase transition.
    Biochemistry. 1986 Jul 15;25(14):4141-7 PMID: 3741846
  52. Giant vesicle bilayers composed of mixtures of lipids, cholesterol and polypeptides. Thermomechanical and (mutual) adherence properties.
    Faraday Discuss Chem Soc. 1986;(81):267-80 PMID: 3582617
  53. Temperature dependence of the structural dimensions of the inverted hexagonal (HII) phase of phosphatidylethanolamine-containing membranes.
    Biochemistry. 1989 May 16;28(10):4245-53 PMID: 2765485
  54. The exocytotic fusion pore modeled as a lipidic pore.
    Biophys J. 1992 Oct;63(4):1118-32 PMID: 1420930
  55. Probability of alamethicin conductance states varies with nonlamellar tendency of bilayer phospholipids.
    Biophys J. 1993 Jul;65(1):23-7 PMID: 8369434
  56. 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):7644-51 PMID: 9201905
  57. Lipidic intramembranous particles.
    Nature. 1979 May 10;279(5709):162-3 PMID: 440422
  58. Small concentrations of alamethicin induce a cubic phase in bulk phosphatidylethanolamine mixtures.
    Biochim Biophys Acta. 1996 Jan 31;1278(2):241-6 PMID: 8593282
  59. Accelerated formation of cubic phases in phosphatidylethanolamine dispersions.
    Biophys J. 1998 Aug;75(2):853-66 PMID: 9675186
  60. 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):402-14 PMID: 8161694
  61. Molecular organization and stability of hydrated dispersions of headgroup-modified phosphatidylethanolamine analogues.
    Biochemistry. 1991 Jul 23;30(29):7212-9 PMID: 1854731
  62. 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):4826-44 PMID: 4074661
  63. Elastic properties of lipid bilayers: theory and possible experiments.
    Z Naturforsch C. 1973 Nov-Dec;28(11):693-703 PMID: 4273690
  64. 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):3901-8 PMID: 9521711
  65. Interaction of the influenza hemagglutinin fusion peptide with lipid bilayers: area expansion and permeation.
    Biophys J. 1997 Sep;73(3):1430-9 PMID: 9284310
  66. The influence of cholesterol on phospholipid membrane curvature and bending elasticity.
    Biophys J. 1997 Jul;73(1):267-76 PMID: 9199791
  67. Lipid polymorphism of mixtures of dioleoylphosphatidylethanolamine and saturated and monounsaturated phosphatidylcholines of various chain lengths.
    Biochemistry. 1987 Jan 13;26(1):231-6 PMID: 3828299
  68. The neutral area surface of the cubic mesophase: location and properties.
    Biophys J. 1994 Feb;66(2 Pt 1):377-81 PMID: 8161691
Article Info
Journal
Biophysical journal
Abbr.
Biophys J
ISSN
0006-3495
DOI
10.1016/S0006-3495(99)77197-3
Email
dsiegel@chemistry.ohio-state.edu
Published
1999-01-00
Pages
291-313
Language
English
Region
United States
NLM ID
0370626
PMCID
PMC1302519
Subset
IM
Grants
NIGMS NIH HHS · GM56969 · United States
External Links
PubMed source DOI: 10.1016/S0006-3495(99)77197-3 PMC Full Text View journal details
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