Phospholipid membranes decorated by cholesterol-based oligonucleotides as soft hybrid nanostructures

Artikel i vetenskaplig tidskrift, 2008

DNA monomers and oligomers are currently showing great promise as building blocks for supramolecular arrays that can self-assemble in a fashion preprogrammed by the base pairing code. The design and build-up of hybrid DNA/amphiphilic self-assemblies can expand the range of possible architectures and enhance the selectivity toward a well-specified geometry. We report on the self-assembly properties in aqueous solution of a cholesteryl-tetraethylenglycol single stranded 18-mer oligonucleotide (ON(1)TEG-Chol) and on its spontaneous insertion in fluid phospholipid membranes. Up to 500 units of these lipophilic ss-oligonucleotides can be incorporated in the outer leaflet of 350 A radius POPC vesicle. The insertion and hybridization with the complementary oligonucleotide are monitored through light scattering as an increase of hydrodynamic thickness, which is interpreted in terms of average distance between anchoring sites. The conformation of the ss-oligonucleotidic portion is strongly dependent on surface coverage, passing from a quasi-random coil to a more rigid configuration, as concentration increases. Interestingly, conformational details affect in a straightforward fashion the hybridization kinetics. Liposomes with single- and double-strand decorations remain stable within the experimental time window (about one week). The structure represents an example of successful and stable amphiphile/DNA supramolecular hybrid, where a DNA guest is held in a membrane by hydrophobic interactions. The lipophilic oligonucleotide under investigation is therefore a suitable building block that can effectively serve as a hydrophobic anchor in the fluid bilayer to assemble supramolecular constructs based on the DNA digital code.