Mechanistic Influence of Nanometer Length-Scale Surface Chemistry on DNA Hybridization
Hybridization of surface-immobilized oligonucleotides to their complementary counterparts is central to the rational design of novel nanodevices and DNA sensors. In this study, we have adopted a unified approach of combining sensing experiments with molecular dynamics simulations to characterize the hybridization of a 23 nucleotide long single-strand probe DNA tethered to a gold surface. Experiments indicate significant conformational changes of DNA in close vicinity (∼1 nm) of the gold surface upon hybridization and also conformational heterogeneity within hybridized DNA, consistent with simulation results. Simulations show that the conformational heterogeneity on a gold surface arises due to stabilization of surface-adsorbed partial and full duplexes, resulting in impeded hybridization in comparison to what observed on a repulsive surface. Furthermore, these simulations indicate that hybridization could be improved by tuning the nonspecific adsorption on a nanopatterned surface with an optimal patterning length. Simulations were performed on the probe tethered to gold nanodots of varying (2-8 nm) diameter. An improved hybridization of the present probe sequence was only observed for the 6 nm gold dots patterned on a repulsive surface. Results reveal that the 2D nanoconfinement provided by the 6 nm gold dot is optimal for reducing conformational heterogeneity for the specific sequence used in this study. Thus, improved DNA hybridization can be achieved on a gold nanodot patterned repulsive surface, where the optimal dot diameter will depend on the probe length and sequence. In summary, this study provides mechanistic insights onto hybridization on gold and offers a unique method toward improved hybridization on a nanopatterned surface with an optimized patterning length.