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Surface-structure-regulated cell-membrane penetration by monolayer-protected nanoparticles

Nature Materials volume 7, pages 588595 (2008) | Download Citation

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  • A Corrigendum to this article was published on 20 March 2013

This article has been updated

Abstract

Nanoscale objects are typically internalized by cells into membrane-bounded endosomes and fail to access the cytosolic cell machinery. Whereas some biomacromolecules may penetrate or fuse with cell membranes without overt membrane disruption, no synthetic material of comparable size has shown this property yet. Cationic nano-objects pass through cell membranes by generating transient holes, a process associated with cytotoxicity. Studies aimed at generating cell-penetrating nanomaterials have focused on the effect of size, shape and composition. Here, we compare membrane penetration by two nanoparticle ‘isomers’ with similar composition (same hydrophobic content), one coated with subnanometre striations of alternating anionic and hydrophobic groups, and the other coated with the same moieties but in a random distribution. We show that the former particles penetrate the plasma membrane without bilayer disruption, whereas the latter are mostly trapped in endosomes. Our results offer a paradigm for analysing the fundamental problem of cell-membrane-penetrating bio- and macro-molecules.

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Change history

  • 28 February 2013

    In the version of this Article originally published, in the caption for Fig. 1 the following statement should have been included "Right-hand STM image in panel a reproduced with permission from ref. 30, © 2008 RSC." This error has been corrected in the PDF and HTML versions of the Article.

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Acknowledgements

This work was supported by the National Science Foundation (CAREER Award) and the NHLBI TPEN program (U01-HL080731). F.S. is grateful to the Packard Foundation for their generous award.

This paper is dedicated to A. Mayes in recognition of the mentor role she had for both corresponding authors.

Author information

Affiliations

  1. Department of Materials Science and Engineering, MIT, Massachusetts 02139, USA

    • Ayush Verma
    • , Oktay Uzun
    • , Ying Hu
    • , Suelin Chen
    • , Darrell J. Irvine
    •  & Francesco Stellacci
  2. Department of Chemical Engineering, MIT, Massachusetts 02139, USA

    • Yuhua Hu
  3. Department of Chemistry, MIT, Massachusetts 02139, USA

    • Hee-Sun Han
  4. Department of Biology, MIT, Massachusetts 02139, USA

    • Nicki Watson
  5. Department of Biological Engineering, MIT, Massachusetts 02139, USA

    • Darrell J. Irvine

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Contributions

D.J.I. and F.S. conceived the research question. A.V., O.U., D.J.I. and F.S. designed the experiments and analysed all of the data. The biological experiments were carried out by A.V. and Yu.H.; TEM experiments were carried out by A.V. and N.W., STM by Yi.H. and S.C., nanoparticle synthesis and characterization by O.U. and H.S.H. The paper was written by A.V., O.U., D.J.I. and F.S.

Corresponding authors

Correspondence to Darrell J. Irvine or Francesco Stellacci.

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    Supplementary Information

    Supplementary Figures S1–S15 and Supplementary Table 1

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DOI

https://doi.org/10.1038/nmat2202

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