Nanoparticles stabilised by hydrophilic pentapeptide sheath.

Researchers in the UK have discovered how to coat nanoparticles of gold and silver with peptides. The encapsulated particles are robust and stable in aqueous systems, where the particles can effectively masquerade as proteins, the scientists say.

The finding has potentially important implications for cell biology. By attaching specific recognition molecules to the peptide capsule around the nanoparticles, it should be possible to follow the fate of individual molecules in a cell over a period of time. The particles persist effectively indefinitely (unlike fluorescent dyes, for example), and are easily detectable by optical microscopy techniques. Furthermore, the particles can be freeze-dried and stored as powders that can be subsequently dissolved to yield stable aqueous dispersions, making the system relatively straightforward to formulate for routine use in the laboratory.

Postdoctoral researcher Raphael Lévy and colleagues at Liverpool University's Centre for Nanoscale Science, based their technique on a previous model developed by the centre. Ten years ago, researchers at the centre found a way to stabilise gold nanoparticles in non-aqueous solutions. This involved using thiol groups as a 'hook' to the surface of the gold, with hydrocarbon tails to encapsulate the particle.

For the new system, the researchers experimented with the thiol-containing amino acid cysteine as the initial anchor to the gold surface. If cysteine is used, it binds to the gold but the particles precipitate irreversibly. So the researchers rationally designed a pentapeptide that would simultaneously bind the gold and stabilise it.

The pentapeptide was constructed with a cysteine residue at the C-terminus, providing the thiol group for the covalent bond with the surface of the gold. Alanine and leucine residues in positions two and three possess hydrophobic side chains, promoting the formation of a stable shell around the particle. The leucine side chain is longer than that of alanine which accounts for the curvature of the particle. Two asparagine residues in positions four and five complete the pentapeptide. The hydrophilicity of this amino acid confers solubility on the particle.

'We have shown that these particles are extremely robust and stable,' says team member Mathias Brust. 'We are now experimenting with attaching a range of recognition motifs to the peptide shell - molecules such as sugars, DNA and antibodies.' It should be relatively straightforward to attach recognition molecules to the particles to enable them to home in on specific structures in a cell, such as protein receptors. 'In this way it should be possible to track a whole range of cellular processes at the level of the single molecule,' says Brust.

The team has successfully repeated the work with silver nanoparticles, which have different optical properties to gold.

Simon Hadlington