The Structure of Short and Genomic DNA at the Interparticle Junctions of Cationic Nanoparticles

Current understanding of the mechanisms underlying noncovalent interac- tions between native DNA and nanoparticles, as well as their impact on the double-helix structure, is far from providing a comprehensive view. It is known that these interactions are largely defined by the physicochemical properties of the metal/liquid interface, in particular by the nanoparticle surface charge. Remarkably, while DNA unzipping upon binding with cationic nanoparticles is reported, the exact determinants of this struc- tural perturbation remain unclear. Herein, plasmon-based spectroscopies (surface-enhanced Raman scattering (SERS) and surface-plasmon reso- nance (SPR) and theoretical simulations are combined to directly inves- tigate the role of the cooperative binding of cationic nanoparticles with different surface charges on the structural integrity of a large variety of DNAs. The intrinsic nature of the SERS effect unlocks the possibility of selectively examining the impact of nanoparticle clustering on the duplex structure over a wide degree of colloidal aggregation and without the need of external intercalating dyes or strand labeling. This extensive work pro- vides new fundamental insights into the interaction between nucleic acids and nanoparticles, addressing key questions regarding the role played by multiple variables such as the nanoparticle surface charge, the DNA-medi- ated cluster size and geometry, and nucleic acids’ length, composition, and conformational properties.