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:

Artificial transmembrane ion channels from self-assembling peptide nanotubes

Abstract

NATURALLY occurring membrane channels and pores are formed from a large family of diverse proteins, peptides and organic secon-dary metabolites whose vital biological functions include control of ion flow, signal transduction, molecular transport and produc-tion of cellular toxins. But despite the availability of a large amount of biochemical information about these molecules1, the design and synthesis of artificial systems that can mimic the bio-logical function of natural compounds remains a formidable task2–12. Here we present a simple strategy for the design of artifi-cial membrane ion channels based on a self-assembled cylindrical β-sheet peptide architecture13. Our systems—essentially stacks of peptide rings—display good channel-mediated ion-transport activ-ity with rates exceeding 107 ions s−1, rivalling the performance of many naturally occurring counterparts. Such molecular assemblies should find use in the design of novel cytotoxic agents, membrane transport vehicles and drug-delivery systems.

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

Similar content being viewed by others

References

  1. Hille, B. Ionic Channels of Excitable Membranes 2nd edn. (Sinauer Associates, Sunderland, 1992).

    Google Scholar 

  2. Montal, M. FASEB J. 4, 2623–2635 (1990).

    Article  CAS  Google Scholar 

  3. Akerfeldt, K. S., Lear, J. D., Wasserman, Z. R., Chung, L. A. & DeGrado, W.F. Acc. Chem. Res. 26, 191–197 (1993).

    Article  CAS  Google Scholar 

  4. Fyles, T. M., James, T. D. & Kaye, K. C. J. Am. chem. Soc. 115, 12315–12321 (1993).

    Article  CAS  Google Scholar 

  5. Roks, M. F. M. & Nolte, R. J. M. Macromolecules 25, 5398–5407 (1992).

    Article  ADS  CAS  Google Scholar 

  6. Pregel, M. J., Jullien, L. & Lehn, J.-M. Angew. Chem. 104, 1695 (1992); Angew. Chem. int. Edn engl. 31, 1637–1640 (1992).

    Article  CAS  Google Scholar 

  7. Anzai, K. et al. Biochim. biophys. Acta 1064, 256–266 (1991).

    Article  CAS  Google Scholar 

  8. Grove, A., Mutter, M., Rivier, J. E. & Montal, M. J. Am. chem. Soc. 115, 5919–5924 (1993).

    Article  CAS  Google Scholar 

  9. Spencer, D. M., Wandless, T. J., Schreiber, S. L. & Crabtree, G. R. Science 262, 1019–1024 (1993).

    Article  ADS  CAS  Google Scholar 

  10. Montal, M., Montal, M. S. & Tomich, J. M. Proc. natn. Acad. Sci. U.S.A. 87, 6929–6933 (1990).

    Article  ADS  CAS  Google Scholar 

  11. Fuhrhop, J.-H., Liman, U. & Koesling J. Am. chem. Soc. 110, 6840–6845 (1988).

    Article  CAS  Google Scholar 

  12. Nakano, A., Xie, Q., Mallen, J. V., Echegoyen, L. & Gokel, G. W. J. Am. chem. Soc. 112, 1287–1289 (1990).

    Article  CAS  Google Scholar 

  13. Ghadiri, M. R., Granja, J. R., Milligan, R. A., McRee, D. E. & Kazanovich, N. Nature 366, 324–327 (1993).

    Article  ADS  CAS  Google Scholar 

  14. Khazanovich, N., Granja, J. R., McRee, D. E., Milligan, R. A. & Ghadiri, M. R. J. Am. Chem. Soc. (in the press).

  15. Engelman, D. M. & Steitz, T. A. Cell 23, 411–422 (1981).

    Article  CAS  Google Scholar 

  16. Rovero, P., Quartara, L. & Fabbri, G. Tetrahedron Lett. 32, 2639–2642 (1991).

    Article  CAS  Google Scholar 

  17. Allen, L. C. Proc. natn. Acad. Sci. U.S.A. 72, 4701–4705 (1975).

    Article  ADS  CAS  Google Scholar 

  18. Engelman, D. M., Steitz, T. A. & Goldman, A. A. Rev. Biophys. biophys. Chem. 15, 321–353 (1986).

    Article  CAS  Google Scholar 

  19. Nabedryk, E., Gingold, M. P. & Breton, J. Biophys. J. 38, 243–249 (1982).

    Article  ADS  CAS  Google Scholar 

  20. Carmichael, V. E. et al. J. Am. chem. Soc. 111, 767–769 (1989).

    Article  CAS  Google Scholar 

  21. Weinstein, J. N., Yoshikami, S., Henkart, P., Blumenthal, R. & Hagins, W. A. Science 195, 489–492 (1977).

    Article  ADS  CAS  Google Scholar 

  22. Jayasuriya, N., Bosak, S. & Regen, S. L. J. Am. chem,. Soc. 112, 5844–5850 (1990).

    Article  CAS  Google Scholar 

  23. Clement, N. R. & Gould, J. M. Biochemistry 20, 1539–1543 and 1544–1548 (1981).

    Article  CAS  Google Scholar 

  24. Suarez-Isla, B. A., Lindstrom, W. K. & Montal, M. Biochemistry 22, 2319–2323 (1983).

    Article  CAS  Google Scholar 

  25. Läuger, P. Angew. Chem. 97, 939–959 (1985); Angew. Chem. int. Edn engl. 24, 905–923 (1985).

    Article  Google Scholar 

  26. Bamberg, E. & Laüger, P. Biochim. biophys. Acta 367, 127–133 (1974).

    Article  CAS  Google Scholar 

  27. Szoka, F. & Papahadjopoulos, D. Proc. natn. Acad. Sci. U.S.A. 75, 4194–4198 (1978).

    Article  ADS  CAS  Google Scholar 

  28. Olson, F., Hunt, C. A., Szoka, F. C., Vail, W. J. & Papahadjopoulos, D. Biochim. biophys. Acta 557, 9–23 (1979).

    Article  CAS  Google Scholar 

  29. New, R. R. C., (ed.) Liposomes (Oxford Univ. Press, 1990).

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ghadiri, M., Granja, J. & Buehler, L. Artificial transmembrane ion channels from self-assembling peptide nanotubes. Nature 369, 301–304 (1994). https://doi.org/10.1038/369301a0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/369301a0

This article is cited by

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

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