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

Nat Mater. 2008 Jul;7(7):588-95. doi: 10.1038/nmat2202. Epub 2008 May 25.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Biological Transport, Active
  • Cell Line
  • Cell Membrane / metabolism*
  • Cell Membrane Permeability
  • Coated Materials, Biocompatible / chemistry
  • Dendritic Cells / metabolism
  • Dendritic Cells / ultrastructure
  • Endocytosis
  • Gold / chemistry
  • Hydrophobic and Hydrophilic Interactions
  • Metal Nanoparticles* / chemistry
  • Mice
  • Microscopy, Electron, Transmission
  • Nanotechnology
  • Particle Size
  • Surface Properties


  • Coated Materials, Biocompatible
  • Gold