Structure and energy of fusion stalks: the role of membrane edges (original) (raw)

Abstract

Fusion of lipid bilayers proceeds via a sequence of distinct structural transformations. Its early stage involves a localized, hemifused intermediate in which the proximal but not yet the distal monolayers are connected. Whereas the so-called stalk model most successfully accounts for the properties of the hemifused intermediate, there is still uncertainty about its microscopic structure and energy. We reanalyze fusion stalks using the theory of membrane elasticity. In our calculations, a short (cylindrical micelle-like) tether connects the two proximal monolayers of the hemifused membranes. The shape of the stalk and the length of the tether are calculated such as to minimize the overall free energy and to avoid the formation of voids within the hydrocarbon core. Our free energy expression is based on three internal degrees of freedom of a perturbed lipid layer: thickness, splay, and tilt deformations. Based on exactly the same model, we compare fusion stalks with and without the ability included to form sharp edges at the interfacial region between the hydrocarbon core and the polar environment. Requiring the interface to be smooth everywhere, our detailed calculations recover previous results: the stalk energies are far too high to account for the experimental observation of fusion intermediates. However, if we allow the interface to be nonsmooth, we find a remarkable reduction of the stalk free energy down to more realistic values. The corresponding structure of a nonsmooth stalk exhibits sharp edges at the transition regions between the bilayer and tether parts. In addition to that, a corner is formed at each of the two distal monolayers. We discuss the mechanism how membrane edges reduce the energy of fusion stalks.

Full Text

The Full Text of this article is available as a PDF (245.9 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. Basáez G., Ruiz-Argüello M. B., Alonso A., Goñi F. M., Karlsson G., Edwards K. Morphological changes induced by phospholipase C and by sphingomyelinase on large unilamellar vesicles: a cryo-transmission electron microscopy study of liposome fusion. Biophys J. 1997 Jun;72(6):2630–2637. doi: 10.1016/S0006-3495(97)78906-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Burger K. N. Greasing membrane fusion and fission machineries. Traffic. 2000 Aug;1(8):605–613. doi: 10.1034/j.1600-0854.2000.010804.x. [DOI] [PubMed] [Google Scholar]
  4. Chanturiya A., Chernomordik L. V., Zimmerberg J. Flickering fusion pores comparable with initial exocytotic pores occur in protein-free phospholipid bilayers. Proc Natl Acad Sci U S A. 1997 Dec 23;94(26):14423–14428. doi: 10.1073/pnas.94.26.14423. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Chernomordik L. V., Leikina E., Frolov V., Bronk P., Zimmerberg J. An early stage of membrane fusion mediated by the low pH conformation of influenza hemagglutinin depends upon membrane lipids. J Cell Biol. 1997 Jan 13;136(1):81–93. doi: 10.1083/jcb.136.1.81. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. 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]
  7. 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]
  8. 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]
  9. Epand R. M. Membrane fusion. Biosci Rep. 2000 Dec;20(6):435–441. doi: 10.1023/a:1010498618600. [DOI] [PubMed] [Google Scholar]
  10. Evans E, Rawicz W. Entropy-driven tension and bending elasticity in condensed-fluid membranes. Phys Rev Lett. 1990 Apr 23;64(17):2094–2097. doi: 10.1103/PhysRevLett.64.2094. [DOI] [PubMed] [Google Scholar]
  11. Gaudin Y. Rabies virus-induced membrane fusion pathway. J Cell Biol. 2000 Aug 7;150(3):601–612. doi: 10.1083/jcb.150.3.601. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. 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]
  13. Jahn R., Südhof T. C. Membrane fusion and exocytosis. Annu Rev Biochem. 1999;68:863–911. doi: 10.1146/annurev.biochem.68.1.863. [DOI] [PubMed] [Google Scholar]
  14. Kozlov M. M., Markin V. S. Vozmozhnyi mekhanizm sliiania membran. Biofizika. 1983 Mar-Apr;28(2):242–247. [PubMed] [Google Scholar]
  15. Kozlovsky Yonathan, Kozlov Michael M. Stalk model of membrane fusion: solution of energy crisis. Biophys J. 2002 Feb;82(2):882–895. doi: 10.1016/S0006-3495(02)75450-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Kuzmin P. I., Zimmerberg J., Chizmadzhev Y. A., Cohen F. S. A quantitative model for membrane fusion based on low-energy intermediates. Proc Natl Acad Sci U S A. 2001 Jun 12;98(13):7235–7240. doi: 10.1073/pnas.121191898. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Lee J., Lentz B. R. Evolution of lipidic structures during model membrane fusion and the relation of this process to cell membrane fusion. Biochemistry. 1997 May 27;36(21):6251–6259. doi: 10.1021/bi970404c. [DOI] [PubMed] [Google Scholar]
  18. Lentz B. R., Malinin V., Haque M. E., Evans K. Protein machines and lipid assemblies: current views of cell membrane fusion. Curr Opin Struct Biol. 2000 Oct;10(5):607–615. doi: 10.1016/s0959-440x(00)00138-x. [DOI] [PubMed] [Google Scholar]
  19. MacKintosh FC, Lubensky TC. Orientational order, topology, and vesicle shapes. Phys Rev Lett. 1991 Aug 26;67(9):1169–1172. doi: 10.1103/PhysRevLett.67.1169. [DOI] [PubMed] [Google Scholar]
  20. Markin Vladislav S., Albanesi Joseph P. Membrane fusion: stalk model revisited. Biophys J. 2002 Feb;82(2):693–712. doi: 10.1016/S0006-3495(02)75432-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. May S., Ben-Shaul A. Molecular theory of lipid-protein interaction and the Lalpha-HII transition. Biophys J. 1999 Feb;76(2):751–767. doi: 10.1016/S0006-3495(99)77241-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. May S. Protein-induced bilayer deformations: the lipid tilt degree of freedom. Eur Biophys J. 2000;29(1):17–28. doi: 10.1007/s002490050247. [DOI] [PubMed] [Google Scholar]
  23. Seifert U, Shillcock J, Nelson P. Role of Bilayer Tilt Difference in Equilibrium Membrane Shapes. Phys Rev Lett. 1996 Dec 23;77(26):5237–5240. doi: 10.1103/PhysRevLett.77.5237. [DOI] [PubMed] [Google Scholar]
  24. 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]
  25. Siegel D. P. The modified stalk mechanism of lamellar/inverted phase transitions and its implications for membrane fusion. Biophys J. 1999 Jan;76(1 Pt 1):291–313. doi: 10.1016/S0006-3495(99)77197-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Zimmerberg J., Vogel S. S., Chernomordik L. V. Mechanisms of membrane fusion. Annu Rev Biophys Biomol Struct. 1993;22:433–466. doi: 10.1146/annurev.bb.22.060193.002245. [DOI] [PubMed] [Google Scholar]