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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.

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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.

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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.

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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.

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Correspondence to Luca Monticelli.

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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

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