DNA-Functionalized Gold Nanoparticles with Toehold-Mediated Strand Displacement for Nucleic Acid Sensors

We present a study of gold nanoparticles linked by DNA that undergo toehold-mediated strand displacement for nucleic acid sensing. The factors influencing colloidal aggregation, thermal melting, and target-induced disassembly were investigated in relation to the surface density of DNA by incorporating diluent DNA. Contrary to conventional expectation, decreasing the surface density of DNA on both sets of particles did not yield the fastest kinetics. By understanding how the surface density of DNA modulates the cooperativity and attinebility of the oligonucleotides, the accessibility of the linkers to the target nucleic acid, and the repulsion between the nanoparticles, we demonstrate that the optimal combination of surface densities for rapid nanoparticle disassembly is one that facilitates target hybridization while maintaining a high repulsive force. The resultant 9-fold acceleration in the reaction enabled the design of nucleic acid sensors based on discrete nanoparticle assemblies. Our work provides insight into the strand-displacement reaction on nanoparticle surfaces that underpins various sensing and DNA-driven nanomachine applications.