Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter
  • Published:

Tension-induced fusion of bilayer membranes and vesicles

Nature Materials volume 4, pages 225–228 (2005)Cite this article

Abstract

Maintaining the integrity of their protective plasma membrane is a primary requirement of cells. Accordingly, cellular events that breach the membrane are tightly regulated1. Artificial vesicles used in drug delivery must also stay intact until they have reached the desired target2. In both cases, the intrinsic resistance of the membrane to rupture must be overcome to allow the efflux of the vesicle's contents. Here, we use mesoscopic simulations3 to study the fusion of 28-nm-diameter vesicles to 50 × 50 nm2 planar membrane patches over 2 μs. We monitor the time evolution of 93 different fusion attempts. This allows us to construct a global morphology diagram, using the initial tensions of the vesicle and the planar membrane patch as control parameters, and to determine the corresponding fusion statistics. All successful fusion events are observed to occur within 350 ns, which reflects the presence of alternative pathways for the tension relaxation.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Adhesion of a tensionless vesicle and membrane.
Figure 2: Fusion event between a vesicle and membrane.
Figure 3: Morphology diagram for a vesicle in close proximity to a planar membrane.
Figure 4: Histogram of the 42 out of 93 independent simulations that result in a fusion pore appearing in a given time.

Similar content being viewed by others

References

  1. Alberts, B. et al. Molecular Biology of the Cell 2nd edn (Garland, New York, 1989).

    Google Scholar 

  2. Lasic, D. D. in Vesicles (ed. Rosoff, M.) Ch. 10 (Surfactant Science Series vol. 62, Marcel Dekker, New York, 1995).

    Google Scholar 

  3. Shillcock, J. C. & Lipowsky, R. Equilibrium structure and lateral stress distribution of amphiphilic bilayers from dissipative particle dynamics. J. Chem. Phys. 117, 5048–5061 (2002).

    Article  CAS  Google Scholar 

  4. Jahn, R. & Grubmüller, H. Membrane fusion. Curr. Opin. Cell Biology 14, 488–495 (2002).

    Article  CAS  Google Scholar 

  5. Mayer, A. Membrane fusion in eukaryotic cells. Annu. Rev. Cell. Dev. Biol. 18, 289–314 (2002).

    Article  CAS  Google Scholar 

  6. Lindau, M. & de Toledo, G. A. The fusion pore. Biochim. Biophys. Acta 1641, 167–173 (2003).

    Article  CAS  Google Scholar 

  7. Ohta-lino, S. et al. Fast lipid disorientation at the onset of membrane fusion revealed by moleculer Dynamics simulations. Biophys. J. 81, 217–224 (2001).

    Article  Google Scholar 

  8. Marrink, S. J. & Mark, A. E. The mechanism of vesicle fusion as revealed by molecular dynamics simulations. J. Am. Chem. Soc. 125, 11144–11145 (2003).

    Article  CAS  Google Scholar 

  9. Stevens, M. J., Hoh, J. H. & Woolf, T. B. Insights into the molecular mechanism of membrane fusion from simulation: evidence for the association of splayed tails. Phys. Rev. Lett. 91, 188102 (2003).

    Article  Google Scholar 

  10. Chanturiya, A., Scaria, P., Kuksenok, O. & Woodle, M. C. Probing the mechanism of fusion in a two-dimensional computer simulation. Biophys. J. 82, 3072–3080 (2002).

    Article  CAS  Google Scholar 

  11. Noguchi, H. & Takasu, M. Fusion pathways of vesicles: a Brownian dynamics simulation. J. Chem. Phys. 115, 9547–9551 (2001).

    Article  CAS  Google Scholar 

  12. Siegel, D. P. The modified stalk mechanism of lamellar/inverted phase transitions and its implications for membrane fusion. Biophys. J. 76, 291–313 (1999).

    Article  CAS  Google Scholar 

  13. Markin, V. S. & Albanesi, J. P. Membrane fusion: stalk model revisited. Biophys. J. 82, 693–712 (2002).

    Article  CAS  Google Scholar 

  14. Mueller, M., Katsov, K. & Schick, M. A new mechanism of model membrane fusion determined from Monte Carlo simulation. Biophys. J. 85, 1611–1623 (2003).

    Article  CAS  Google Scholar 

  15. Hoogerbrugge, P. J. & Koelman, J. M. V. A. Simulating microscopic hydrodynamic phenomena with dissipative particle dynamics. Europhys. Lett. 19, 155–160 (1992).

    Article  Google Scholar 

  16. Kranenburg, M., Venturoli, M. & Smit, B. Molecular simulations of mesoscopic bilayer phases. Phys. Rev. E. 67, 060901 (2003).

    Article  Google Scholar 

  17. Yamamoto, S., Maruyama, Y. & Hyodo, S. Dissipative particle dynamics study of spontaneous vesicle formation of amphiphilic molecules. J. Chem. Phys. 116, 5842–5849 (2002).

    Article  CAS  Google Scholar 

  18. Groot, R. D. & Warren, P. B. Dissipative particle dynamics: bridging the gap between atomistic and mesoscopic simulation. J. Chem. Phys. 107, 4423–4435 (1997).

    Article  CAS  Google Scholar 

  19. Vattulainen, I., Karttunen, M., Besold, G. & Polson, J. M. Integration schemes for dissipative particle dynamics simulations: from softly interacting systems to hybrid models. J. Chem. Phys. 116, 3967–3979 (2002).

    Article  CAS  Google Scholar 

  20. Warren, P. B. Dissipative particle dynamics. Curr. Opin. Colloid Interface Sci. 3, 620–624 (1998).

    Article  CAS  Google Scholar 

  21. Nielsen, S. O., Lopez, C. F., Srinivas, G. & Klein, M. L. Coarse grain models and the computer simulation of soft materials. J. Phys. Chem. B. 108, 8153–8160 (2004).

    Article  Google Scholar 

  22. McNew, J. A. et al. Close is not enough: SNARE-dependent membrane fusion requires an active mechanism that transduces force to membrane anchors. J. Cell Biol. 150, 105–117 (2000).

    Article  CAS  Google Scholar 

  23. Yersin, A. et al. Interactions between synaptic vesicle fusion proteins explored by atomic force microscopy. Proc. Natl Acad. Sci. USA 100, 8736–8741 (2003).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank Erwin Neher for helpful correspondence and acknowledge support by the Human Frontier Science Project through research grant RGP0072/2003. We also thank one of the reviewers for their rather detailed comments on the first version of this manuscript.

Author information

Authors and Affiliations

  1. Max Planck Institute of Colloids and Interfaces, Potsdam, 14424, Germany

    Julian C. Shillcock & Reinhard Lipowsky

Authors
  1. Julian C. Shillcock
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Reinhard Lipowsky
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Reinhard Lipowsky.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Information

Supplementary figures S1 and S2; table S1 (PDF 3569 kb)

Supplementary Information

Supplementary movie (E) (MOV 3083 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Shillcock, J., Lipowsky, R. Tension-induced fusion of bilayer membranes and vesicles. Nature Mater 4, 225–228 (2005). https://doi.org/10.1038/nmat1333

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nmat1333

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing