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

A Corrigendum to this article was published on 20 March 2013

This article has been updated


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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Figure 1: Nanoparticles with ordered arrangements of hydrophilic and hydrophobic surface functional groups exhibit altered patterns of subcellular localization in cells.
Figure 2: ‘Striped’ nanoparticles enter cells at 37 C under conditions where active internalization processes are blocked.
Figure 3: Nanoparticles with sulphonate-only or disordered sulphonate/methyl-group surfaces are largely confined to endosomal compartments, whereas ‘striped’ sulphonate/methyl-group-bearing nanoparticles enter the cytosol.
Figure 4: ‘Striped’ particles visualized at different stages of crossing the cell membrane of dendritic cells.
Figure 5: ‘Striped’ nanoparticles penetrate cell membranes without generating transient holes, in contrast with the known behaviour of cationic nanoparticles.

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  • 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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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.

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Authors and Affiliations



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.

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Correspondence to Darrell J. Irvine or Francesco Stellacci.

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Supplementary Figures S1–S15 and Supplementary Table 1 (PDF 878 kb)

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Verma, A., Uzun, O., Hu, Y. et al. Surface-structure-regulated cell-membrane penetration by monolayer-protected nanoparticles. Nature Mater 7, 588–595 (2008).

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