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.

Computer simulation study of fullerene translocation through lipid membranes

Abstract

Recent toxicology studies suggest that nanosized aggregates of fullerene molecules can enter cells and alter their functions, and also cross the blood–brain barrier. However, the mechanisms by which fullerenes penetrate and disrupt cell membranes are still poorly understood. Here we use computer simulations to explore the translocation of fullerene clusters through a model lipid membrane and the effect of high fullerene concentrations on membrane properties. The fullerene molecules rapidly aggregate in water but disaggregate after entering the membrane interior. The permeation of a solid-like fullerene aggregate into the lipid bilayer is thermodynamically favoured and occurs on the microsecond timescale. High concentrations of fullerene induce changes in the structural and elastic properties of the lipid bilayer, but these are not large enough to mechanically damage the membrane. Our results suggest that mechanical damage is an unlikely mechanism for membrane disruption and fullerene toxicity.

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

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

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

Figure 1: Kinetics of fullerene permeation.
Figure 2: Mechanism of permeation of fullerene through a lipid membrane.
Figure 3: Structural properties of the membrane during fullerene permeation.
Figure 4: Distribution of fullerene in the membrane.

Similar content being viewed by others

References

  1. Murayama, H., Tomonoh, S., Alford, J. M. & Karpuk, M. E. Fullerene production in tons and more: From science to industry. Fuller. Nanotub. Carbon Nanostruct. 12, 1–9 (2004).

    Article  Google Scholar 

  2. Colvin, V. L. The potential environmental impact of engineered nanomaterials. Nature Biotechnol. 21, 1166–1170 (2003).

    Article  Google Scholar 

  3. Oberdorster, G., Ferin, J. & Lehnert, B. E. Correlation between particle size, in vivo particle persistence, and lung injury. Environ. Health Perspect. 102 (suppl. 5), 173–179 (1994).

    Google Scholar 

  4. Oberdorster, G. et al. Translocation of inhaled ultrafine particles to the brain. Inhal. Toxicol. 16, 437–445 (2004).

    Article  Google Scholar 

  5. Oberdorster, G., Oberdorster, E. & Oberdorster, J. Nanotoxicology: an emerging discipline evolving from studies of ultrafine particles. Environ. Health Perspect. 113, 823–839 (2005).

    Article  Google Scholar 

  6. Fortner, J. D. et al. C-60 in water: Nanocrystal formation and microbial response. Environ. Sci. Technol. 39, 4307–4316 (2005).

    Article  Google Scholar 

  7. Lyon, D. Y., Adams, L. K., Falkner, J. C. & Alvarez, P. J. J. Antibacterial activity of fullerene water suspensions: Effects of preparation method and particle size. Environ. Sci. Technol. 40, 4360–4366 (2006).

    Article  Google Scholar 

  8. Oberdorster, E. Manufactured nanomaterials (fullerenes, C60) induce oxidative stress in the brain of juvenile largemouth bass. Environ. Health Perspect. 112, 1058–1062 (2004).

    Article  Google Scholar 

  9. Andrievsky, G., Klochkov, V. & Derevyanchenko, L. Is the C-60 fullerene molecule toxic? Fuller. Nanotub. Carbon Nanostruct. 13, 363–376 (2005).

    Article  Google Scholar 

  10. Sayes, C. M. et al. The differential cytotoxicity of water-soluble fullerenes. Nano Lett. 4, 1881–1887 (2004).

    Article  Google Scholar 

  11. Sayes, C. M. et al. Nano-C60 cytotoxicity is due to lipid peroxidation. Biomaterials 26, 7587–7595 (2005).

    Article  Google Scholar 

  12. Wang, I. C. et al. C-60 and water-soluble fullerene derivatives as antioxidants against radical-initiated lipid peroxidation. J. Med. Chem. 42, 4614–4620 (1999).

    Article  Google Scholar 

  13. Foley, S. et al. Cellular localisation of a water-soluble fullerene derivative. Biochem. Biophys. Res. Commun. 294, 116–119 (2002).

    Article  Google Scholar 

  14. Venkatesan, N., Yoshimitsu, J., Ito, Y., Shibata, N. & Takada, K. Liquid filled nanoparticles as a drug delivery tool for protein therapeutics. Biomaterials 26, 7154–7163 (2005).

    Article  Google Scholar 

  15. Lopez, C. F., Nielsen, S. O., Moore, P. B. & Klein, M. L. Understanding nature's design for a nanosyringe. Proc. Natl Acad. Sci. USA 101, 4431–4434 (2004).

    Article  Google Scholar 

  16. Srinivas, G. & Klein, M. L. Computational approaches to nanobiotechnology: probing the interaction of synthetic molecules with phospholipid bilayers via a coarse grain model. Nanotechnology 15, 1289–1295 (2004).

    Article  Google Scholar 

  17. Beckstein, O. & Sansom, M. S. Liquid–vapor oscillations of water in hydrophobic nanopores. Proc. Natl Acad. Sci. USA 100, 7063–7068 (2003).

    Article  Google Scholar 

  18. Hummer, G., Rasaiah, J. C. & Noworyta, J. P. Water conduction through the hydrophobic channel of a carbon nanotube. Nature 414, 188–190 (2001).

    Article  Google Scholar 

  19. Choudhury, N. A molecular dynamics simulation study of buckyballs in water: atomistic versus coarse-grained models of C60. J. Chem. Phys. 125, 034502 (2006).

    Article  Google Scholar 

  20. Izvekov, S., Violi, A. & Voth, G. A. Systematic coarse-graining of nanoparticle interactions in molecular dynamics simulation. J. Phys. Chem. B 109, 17019–17024 (2005).

    Article  Google Scholar 

  21. Li, L., Bedrov, D. & Smith, G. D. Repulsive solvent-induced interaction between C60 fullerenes in water. Phys. Rev. E 71, 011502 (2005).

    Article  Google Scholar 

  22. Qiao, R., Roberts, A. P., Mount, A. S., Klaine, S. J. & Ke, P. C. Translocation of C60 and its derivatives across a lipid bilayer. Nano Lett. 7, 614–619 (2007).

    Article  Google Scholar 

  23. Li, L., Davande, H., Bedrov, D. & Smith, G. D. A molecular dynamics simulation study of C60 fullerenes inside a dimyristoylphosphatidylcholine lipid bilayer. J. Phys. Chem. B 111, 4067–4072 (2007).

    Article  Google Scholar 

  24. Marrink, S. J., de Vries, A. H. & Mark, A. E. Coarse grained model for semiquantitative lipid simulations. J. Phys. Chem. B 108, 750–760 (2004).

    Article  Google Scholar 

  25. Marrink, S. J., Risselada, H. J., Yefimov, S., Tieleman, D. P. & de Vries, A. H. The MARTINI forcefield: coarse grained model for biomolecular simulations. J. Phys. Chem. B 111, 7812–7824 (2007).

    Article  Google Scholar 

  26. Monticelli, L. et al. The MARTINI coarse-grained force field: extension to proteins. J. Chem. Theory Comput., doi: 10.1021/ct700324x.

  27. Marrink, S. J. & Berendsen, H. J. C. Permeation process of small molecules across lipid membranes studied by molecular dynamics simulations. J. Phys. Chem. 100, 16729–16738 (1996).

    Article  Google Scholar 

  28. Ruoff, R. S., Tse, D. S., Malhotra, R. & Lorents, D. C. Solubility of C60 in a variety of solvents. J. Phys. Chem. 97, 3379–3383 (1993).

    Article  Google Scholar 

  29. Bemporad, D., Essex, J. W. & Luttmann, C. Permeation of small molecules through a lipid bilayer: A computer simulation study. J. Phys. Chem. B 108, 4875–4884 (2004).

    Article  Google Scholar 

  30. Paula, S., Volkov, A. G., VanHoek, A. N., Haines, T. H. & Deamer, D. W. Permeation of protons, potassium ions, and small polar molecules through phospholipid bilayers as a function of membrane thickness. Biophys. J. 70, 339–348 (1996).

    Article  Google Scholar 

  31. Filippov, A., Oradd, G. & Lindblom, G. The effect of cholesterol on the lateral diffusion of phospholipids in oriented bilayers. Biophys. J. 84, 3079–3086 (2003).

    Article  Google Scholar 

  32. Rawicz, W., Olbrich, K. C., McIntosh, T., Needham, D. & Evans, E. Effect of chain length and unsaturation on elasticity of lipid bilayers. Biophys. J. 79, 328–339 (2000).

    Article  Google Scholar 

  33. Jeng, U. S. et al. Dispersion of fullerenes in phospholipid bilayers and the subsequent phase changes in the host bilayers. Physica B 357, 193–198 (2005).

    Article  Google Scholar 

  34. Ly, H. V. & Longo, M. L. The influence of short-chain alcohols on interfacial tension, mechanical properties, area/molecule, and permeability of fluid lipid bilayers. Biophys. J. 87, 1013–1033 (2004).

    Article  Google Scholar 

  35. Brown, M. F., Thurmond, R. L., Dodd, S. W., Otten, D. & Beyer, K. Elastic deformation of membrane bilayers probed by deuterium NMR relaxation. J. Am. Chem. Soc. 124, 8471–8484 (2002).

    Article  Google Scholar 

  36. Niemelä, P. S., Ollila, S., Hyvonen, M. T., Karttunen, M. & Vattulainen, I. Assessing the nature of lipid raft membranes. PLoS Comput. Biol. 3, 304–312 (2007).

    Article  Google Scholar 

  37. Lundbaek, J. A. Regulation of membrane protein function by lipid bilayer elasticity—a single molecule technology to measure the bilayer properties experienced by an embedded protein. J. Phys. Condens. Matter 18, S1305–S1344 (2006).

    Article  Google Scholar 

  38. McIntosh, T. J. & Simon, S. A. Roles of bilayer material properties in function and distribution of membrane properties. Annu. Rev. Biophys. Biomolec. Struct. 35, 177–198 (2006).

    Article  Google Scholar 

  39. Marcus, Y. et al. Solubility of C60 fullerene. J. Phys. Chem. B 105, 2499–2506 (2001).

    Article  Google Scholar 

  40. Torrie, G. M. & Valleau, J. P. Nonphysical sampling distribution in Monte Carlo free energy estimation: umbrella sampling. J. Comput. Phys. 23, 187–199 (1977).

    Article  Google Scholar 

  41. Kumar, S., Bouzida, D., Swendsen, R. H., Kollman, P. A. & Rosenberg, J. M. The weighted histogram analysis method for free-energy calculations on biomolecules.1. The method. J. Comp. Chem. 13, 1011–1021 (1992).

    Article  Google Scholar 

  42. Marrink, S. J. & Berendsen, H. J. C. Simulation of water transport through a lipid membrane. J. Phys. Chem. 98, 4155–4168 (1994).

    Article  Google Scholar 

  43. Lindahl, E., Hess, B. & van der Spoel, D. GROMACS 3.0: A package for molecular simulation and trajectory analysis. J. Mol. Model. 7, 306–317 (2001).

    Article  Google Scholar 

Download references

Acknowledgements

L.M. thanks M.M. Sperotto for fruitful discussions about membrane elasticity theory. This research was supported by the Natural Sciences and Engineering Research Council of Canada (NSERC). J.W. and I-M.T. are supported by the Royal Golden Jubilee PhD Program (PHD/0240/2545). W.T. is supported by the National Center for Genetic Engineering and Biotechnology (BIOTEC) and Thailand Research Fund (TRF). S.B. is an Alberta Ingenuity postdoctoral fellow, D.P.T. is an Alberta Heritage Foundation for Medical Research (AHFMR) Senior Scholar and Canadian Institutes for Health Research New Investigator, and L.M. is an AHFMR postdoctoral fellow. Calculations were performed in part on WestGrid facilities.

Author information

Authors and Affiliations

Authors

Contributions

L.M. and D.P.T. conceived and designed the simulations. J.W., S.B. and L.M. performed the simulations and analysed the results. W.T., I-M.T. and D.P.T. contributed materials and funding. The paper was written by L.M., with substantial contributions by D.P.T. and J.W. All authors discussed the results and commented on the manuscript.

Corresponding author

Correspondence to Luca Monticelli.

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wong-Ekkabut, J., Baoukina, S., Triampo, W. et al. Computer simulation study of fullerene translocation through lipid membranes. Nature Nanotech 3, 363–368 (2008). https://doi.org/10.1038/nnano.2008.130

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nnano.2008.130

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