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Cell entry of one-dimensional nanomaterials occurs by tip recognition and rotation

Abstract

Materials with high aspect ratio, such as carbon nanotubes and asbestos fibres, have been shown to cause length-dependent toxicity in certain cells because these long materials prevent complete ingestion and this frustrates the cell1,2,3. Biophysical models have been proposed to explain how spheres and elliptical nanostructures enter cells4,5,6,7,8, but one-dimensional nanomaterials have not been examined. Here, we show experimentally and theoretically that cylindrical one-dimensional nanomaterials such as carbon nanotubes enter cells through the tip first. For nanotubes with end caps or carbon shells at their tips, uptake involves tip recognition through receptor binding, rotation that is driven by asymmetric elastic strain at the tube–bilayer interface, and near-vertical entry. The precise angle of entry is governed by the relative timescales for tube rotation and receptor diffusion. Nanotubes without caps or shells on their tips show a different mode of membrane interaction, posing an interesting question as to whether modifying the tips of tubes may help avoid frustrated uptake by cells.

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Figure 1: Experimental evidence for energy-dependent tip-entry mode in the cellular interactions of one-dimensional nanomaterials.
Figure 2: Course-grained molecular dynamics simulation model.
Figure 3: Time sequence of CGMD simulation results showing a MWCNT penetrating the cell membrane at an initial entry angle of θ0 = 45°.
Figure 4: Analytical model of a MWCNT entering cell.

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Acknowledgements

This work was supported by the National Science Foundation (NSF; grant CMMI-1028530), the US Department of Commerce, National Institute of Standards and Technology as part of the Rhode Island Consortium for Nanoscience and Nanotechnology, the National Institute of Environmental Health Sciences (NIEHS) Superfund Research Program P42 ES013660, and an R01 grant (ES016178) from the NIEHS. The simulations reported were performed on NSF TeraGrid resources provided by National Institute for Computational Sciences (NICS; under MCB090194) and resources from the Supercomputing Center of Chinese Academy of Sciences (SCCAS) and Shanghai Supercomputer Center (SSC). The authors thank P. Weston in the Molecular Pathology Core at Brown University for her assistance with electron microscopic sample preparation and imaging and F. Guo for measurement of MWCNT zeta potentials.

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X.H.S., A.v.d.B., R.H.H., A.B.K. and H.J.G. conceived and designed the experiments and simulations. X.H.S. performed the simulations. A.v.d.B. performed the experiments. X.H.S., A.v.d.B., R.H.H., A.B.K. and H.J.G. analysed the data. X.H.S., A.v.d.B., R.H.H., A.B.K. and H.J.G. co-wrote the paper. All authors discussed the results and commented on the manuscript.

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Correspondence to Agnes B. Kane or Huajian Gao.

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Shi, X., von dem Bussche, A., Hurt, R. et al. Cell entry of one-dimensional nanomaterials occurs by tip recognition and rotation. Nature Nanotech 6, 714–719 (2011). https://doi.org/10.1038/nnano.2011.151

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