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:

Self-assembled virus–membrane complexes

Abstract

Anionic polyelectrolytes and cationic lipid membranes can self-assemble into lamellar structures ranging from alternating layers of membranes and polyelectrolytes1,2,3,4,5,6,7,8,9,10,11 to 'missing layer' superlattice structures12. We show that these structural differences can be understood in terms of the surface-charge-density mismatch between the polyelectrolyte and membrane components by examining complexes between cationic membranes and highly charged M13 viruses, a system that allowed us to vary the polyelectrolyte diameter independently of the charge density. Such virus–membrane complexes have pore sizes that are about ten times larger in area than DNA–membrane complexes, and can be used to package and organize large functional molecules; correlated arrays of Ru(bpy)32+ macroionic dyes have been directly observed within the virus–membrane complexes using an electron-density reconstruction. These observations elucidate fundamental design rules for rational control of self-assembled polyelectrolyte–membrane structures, which have applications ranging from non-viral gene therapy13,14,15,16 to biomolecular templates for nanofabrication17.

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

Access options

Buy this article

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

Figure 1: Representation of polyelectrolyte–membrane complexes.
Figure 2: Complexes between highly charged M13 filamentous viruses and cationic membranes.
Figure 3: Organization of nanoscopic arrays of Ru(bpy)32+ macroions by virus–membrane complexes.
Figure 4: Electron density ρ(z) reconstruction of the M13-membrane unit cell.

Similar content being viewed by others

References

  1. Radler, J.O., Koltover, I., Salditt, T. & Safinya, C.R. Structure of DNA-cationic liposome complexes: DNA intercalation in multilamellar membranes in distinct interhelical packing regimes. Science 275, 810–814 (1997).

    Article  CAS  Google Scholar 

  2. Subramanian, G. et al. Structure of complexes of cationic lipids and poly(glutamic acid) polypeptides: A pinched lamellar phase. J. Am. Chem. Soc. 122, 26–34 (2000).

    Article  CAS  Google Scholar 

  3. Ponomarenko, E.A., Waddon, A.J., Bakeev, K.N., Tirrell, D.A. & MacKnight, W.J. Self-assembled complexes of synthetic polypeptides and oppositely charged low molecular weight surfactants solid-state properties. Macromolecules 29, 4340–4345 (1996).

    Article  CAS  Google Scholar 

  4. Antonietti, M., Conrad, J. & Thuenemann, A. Polyelectrolyte-surfactant complexes: A new type of solid mesomorphous material. Macromolecules 27, 6007–6011 (1994).

    Article  CAS  Google Scholar 

  5. Salditt, T., Koltover, I., Radler, J.O. & Safinya, C.R. Two-dimensional smectic ordering of linear DNA chains in self-assembled DNA-cationic liposome mixtures. Phys. Rev. Lett. 79, 2582–2585 (1997).

    Article  CAS  Google Scholar 

  6. Harries, D., May, S., Gelbart, W.M. & Ben-Shaul, A. Structure, stability, and thermodynamics of lamellar DNA-lipid complexes. Biophys. J. 75, 159–173 (1998).

    Article  CAS  Google Scholar 

  7. Golubovic, L. & Golubovic, M. Fluctuations of quasi-two-dimensional smectics intercalated between membranes in multilamellar phases of DNA cationic lipid complexes. Phys. Rev. Lett. 80, 4341–4344 (1998).

    Article  CAS  Google Scholar 

  8. O'Hern, C.S. & Lubensky, T.C. Sliding columnar phase of DNA lipid complexes. Phys. Rev. Lett. 80, 4345–4348 (1998).

    Article  CAS  Google Scholar 

  9. Bruinsma, R. Electrostatics of DNA-cationic lipid complexes: Isoelectric instability. Eur. Phys. J. B 4, 75–88 (1998).

    Article  CAS  Google Scholar 

  10. Bruinsma, R. & Mashl, J. Long-range electrostatic interaction in DNA cationic lipid complexes. Europhys. Lett. 41, 165–170 (1998).

    Article  CAS  Google Scholar 

  11. May, S. & Ben-Shaul, A. DNA-lipid complexes: stability of honeycomb-like and spaghetti-like structures. Biophys. J. 73, 2427–2440 (1997).

    Article  CAS  Google Scholar 

  12. Wong, G.C.L. et al. Hierarchical self-assembly of F-actin and cationic lipid complexes: Stacked three-layer tubule networks. Science 288, 2035–2039 (2000).

    Article  CAS  Google Scholar 

  13. Felgner, P.L. Nonviral strategies for gene therapy. Sci. Am. 276, 102–106 (1997).

    Article  CAS  Google Scholar 

  14. Friedmann, T. Overcoming the obstacles to gene therapy. Sci. Am. 276, 96–101 (1997).

    Article  CAS  Google Scholar 

  15. Lin, A.J. et al. Three-dimensional imaging of lipid gene-carriers: Membrane charge density controls universal transfection behavior in lamellar cationic liposome-DNA complexes. Biophys. J. 84, 3307–3316 (2003).

    Article  CAS  Google Scholar 

  16. Koltover, I., Salditt, T., Radler, J.O. & Safinya, C.R. An inverted hexagonal phase of cationic liposome-DNA complexes related to DNA release and delivery. Science 281, 78–81 (1998).

    Article  CAS  Google Scholar 

  17. Liang, H., Angelini, T.E., Ho, J., Braun, P.V. & Wong, G.C.L. Molecular imprinting of biomineralized CdS nanostructures: Crystallographic control using self-assembled DNA-membrane templates. J. Am. Chem. Soc. 125, 11786–11787 (2003).

    Article  CAS  Google Scholar 

  18. Lasic, D.D., Strey, H., Stuart, M.C.A., Podgornik, R. & Frederik, P.M. The structure of DNA-liposome complexes. J. Am. Chem. Soc. 119, 832–833 (1997).

    Article  CAS  Google Scholar 

  19. Day, L.A., Marzee, C.J., Reisberg, S.A. & Casadevall, A. DNA packing in filamentous bacteriophages. Annu. Rev. Biophys. Biophys. Chem. 17, 509–539 (1988).

    Article  CAS  Google Scholar 

  20. Day, L.A., Marzee, C.J., Reisberg, S.A. & Casadevall, A. DNA packing in filamentous bacteriophages. Ann. Rev. Biophys. Biophys. Chem. 17, 509–539 (1988).

    Article  CAS  Google Scholar 

  21. Koltover, I., Salditt, T. & Safinya, C.R. Phase diagram, stability, and overcharging of lamellar cationic lipid-DNA self-assembled complexes. Biophys. J. 77, 915–924 (1999).

    Article  CAS  Google Scholar 

  22. Koltover, I., Wagner, K. & Safinya, C.R. DNA condensation in two dimensions. Proc. Natl Acad. Sci. USA 97, 14046–14051 (2000).

    Article  CAS  Google Scholar 

  23. Lodish, H. et al. Molecular Cell Biology (Scientific American Books, New York, 1995).

  24. Koltover, I., Sahu, S. & Davis, N. Genetic engineering of the nanoscale structure in polyelectrolyte-lipid self-assmbled systems. Angew. Chem. Int. Edn (in the press).

  25. Stupp, S.I. & Braun, P.V. Molecular manipulation of microstructures: Biomaterials, ceramics, and semiconductors. Science 277, 1242–1248 (1997).

    Article  CAS  Google Scholar 

  26. Kresge, C.T., Leonowicz, M.E., Roth, W.J., Vartuli, J.C. & Beck, J.S. Ordered mesoporous molecular sieves synthesized by a liquid-crystal template mechanism. Nature 359, 710–712 (1992).

    Article  CAS  Google Scholar 

  27. Brinker, C.J. Oriented inorganic films. Curr. Opin. Colloid Interface Sci. 3, 166–173 (1998).

    Article  CAS  Google Scholar 

  28. Monnier, A. et al. Cooperative formation of inorganic-organic interfaces in the synthesis of silicate mesostructures. Science 261, 1299–1303 (1993).

    Article  CAS  Google Scholar 

  29. Mann, S. Biomineralization: Principles and Concepts in Bioinorganic Materials Chemistry (Oxford Univ. Press, New York, 2002).

    Google Scholar 

  30. Hartgerink, J.D., Beniash, E. & Stupp, S.I. Self-assembly and mineralization of peptide-amphiphile nanofibers. Science 294, 1684–1688 (2001).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This material is based upon work supported in part by the US Department of Energy, Division of Materials Sciences under Award No. DEFG02-91ER45439, through the Frederick Seitz Materials Research Laboratory, and carried out in part in the Center for Microanalysis of Materials, which is partially supported by the US Department of Energy under grant DEFG02-91-ER45439, and by NSF-DMR-0409769 and the NSF Nanoscience & Engineering Initiative.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Gerard C. L. Wong.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Yang, L., Liang, H., Angelini, T. et al. Self-assembled virus–membrane complexes. Nature Mater 3, 615–619 (2004). https://doi.org/10.1038/nmat1195

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nmat1195

This article is cited by

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