How curved is your surface--peptides tell all.

Self-assembled monolayers on flat gold surfaces have been well studied for a variety of molecules. One of the unique features of these assemblies is that even weak inter-chain interactions can control the packing of, for example, alkyl thiols, into an almost crystalline array. However, everything changes when the surfaces are curved, as they are in the case of gold nanoparticles. In a recent communication published in the Journal of the American Chemical Society 127 (2007), 6356-6357, chemistry professor and Canada Research Chair in biomaterials, Heinz-Bernhard Kraatz, MCIC, described an in-depth study of the sensitivity of peptide monolayers to the size and structure of the gold surface to which they are attached. In their study, co-authored by graduate student Himadri S. Mandal, MCIC, the University of Saskatoon team showed that even small changes in the size of the nanoparticles to which the peptides are bound can have a dramatic effect on the secondary structures of the peptides.

Kraatz and Mandal chose a peptide containing 16 amino acid residues with a leucine-rich core as a small-molecule mimic of larger peptides. The 16 aa peptide is hydrophobic and tends to adopt an [alpha]-helical conformation. A thiol-containing cysteine residue at the N-terminus provides the point for anchoring to the gold surfaces.

In order to probe the structure of the peptide when bound to the different surfaces, the team examined the amide 1 (carbonyl) and amide A (NH) resonances in the IR spectra, which are indicative of the secondary structure of the peptide. When adsorbed on a flat gold surface, the amide stretch is indicative of an [alpha]-helical structure similar to that observed in the free state. However, everything changes when things get nano.

On gold nanoparticles that are 5 nm in diameter, the IR spectrum changes completely, indicating that as much as 78 percent of the peptide takes up a [beta]-sheet structure. As the size of the nanoparticles increases, the IR spectrum becomes more and more like that on a smooth gold surface. At 10 nm, 48 percent of the peptide assumes a [beta]-sheet structure, and at 20 nm, the spectrum indicates reversion of the peptide to its original [alpha]-helical arrangement (see Figure 1).

[FIGURE 1 OMITTED]

Kraatz and Mandal rationalize these effects by considering the detailed structure of the gold nanoparticles, which are actually polyhedra possessing edges, corners, and faces. As the size of the nanoparticle decreases, the relative proportion of the more reactive edge and corner sites increases. The thiol-terminated peptides aggregate at these more reactive sites, in a more dense arrangement than observed on a pure flat face, which drives the secondary structure to assume the [beta]-sheet orientation. As the degree of curvature of the surface decreases, the more reactive gold sites also decrease in number, and the larger gold nanoparticles assume more of a flat-surface-like structure and reactivity. Since the secondary structure of proteins and peptides is a critical component of their bioactivity, and since peptide-coated nanoparticles are used in a variety of diagnostic and imaging techniques, this study is likely to have a significant impact on chemistry and biology. The Kraatz group will likely continue to unravel these effects in their new home at The University of Western Ontario.