Nanoparticles that can penetrate a cell without causing overt disruption are described online this week in Nature Materials. When covered with two different kinds of molecules in a 'striped' arrangement, these nanoparticles can pass directly through the highly protective barrier of the cell membrane without creating holes leading to cell death. This mechanism could be used to deliver biologically active molecules into the cell for therapeutic purposes.

Although some biomolecules can directly pass through cell membranes, for some time there has been controversy surrounding the possibility of a similar mechanism occurring for synthetic particles of a similar size. Usually, the uptake of synthetic objects into the cell results in them reaching only a limited area within small compartments rather than the main fluid section, called the cytosol, of the cell. Objects, such as positively charged nanoparticles, also create small transient holes that disrupt the membrane in the process and can cause cell death.

MIT researchers show that gold nanoparticles can penetrate the cell membrane without causing disruption, and reach the cytosol if the particles are coated with both negatively charged and hydrophobic ligands arranged in an alternating 'striped' fashion. If these ligands are arranged in a random way, but in the same ratio, on the nanoparticles, the particles can not directly pass through the membrane.

The abstract says:

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 paradigmfor analysing the fundamental problemof cell-membrane-penetrating bio- and macro-molecules.