“Three-Dimensional Hybridization” with Polyvalent DNA−Gold Nanoparticle Conjugates

We have determined the minimum number of base pairings necessary to stabilize DNA−Au NP aggregates as a function of salt concentration for particles between 15 and 150 nm in diameter. Significantly, we find that sequences containing a single base pair interaction are capable of effecting hybridization between 150 nm DNA−Au NPs. While traditional DNA hybridization involves two strands interacting in one dimension (1D, Z), we propose that hybridization in the context of an aggregate of polyvalent DNA−Au NP conjugates occurs in three dimensions (many oligonucleotides oriented perpendicular to the X,Y plane engage in base pairing), making nanoparticle assembly possible with three or fewer base pairings per DNA strand. These studies enabled us to compare the stability of duplex DNA free in solution and bound to the nanoparticle surface. We estimate that 4−8, 6−19, or 8−33 additional DNA bases must be added to free duplex DNA to achieve melting temperatures equivalent to hybridized systems formed from 15, 60, or 150 nm DNA−Au NPs, respectively. In addition, we estimate that the equilibrium binding constant (K_eq) for 15 nm DNA−Au NPs (3 base pairs) is ∼3 orders of magnitude higher than the K_eq for the corresponding nanoparticle free system.