Assemblies of DNA-Functionalized Nanoparticles Respond to Wide Ranges of Salt Concentrations

The assembly and functionality of many biomolecules are coupled to a complex and dynamic solution microenvironment. For example, the effective nature and range of electrostatic forces that mediate interactions between charged objects are determined by (among other factors) the concentrations, types, and distributions of electrolyte ions present in solution. There is a growing body of evidence that the manifestations of electrostatic forces in concentrated solutions can be both counterintuitive and technically useful; thus, studies which help characterize such exotic behavior have the prospect to not only allow for more-informed design of new materials applied in such conditions, but also to open up new degrees of functionality in currently employed synthetic biomaterials. Consider nanoparticles functionalized with DNA, which are often selected for diagnostic or therapeutic applications owing to their capacity for highly selective Watson-Crick base-pairing; such nanoparticles are also highly charged, and thus can serve as responsive probes for changes in the strength and spatial extent of electrostatic interactions in various ionic conditions. In this work, we demonstrate via solution small-angle X-ray scattering (SAXS) that such particles, functionalized with non-base-pairing oligonucleotide sequences, assemble into colloidal crystals in the presence of the biologically relevant Ca²⁺ cation. Our measurements reveal that raising the solution ionic strength induces phase transitions from face-centered cubic (FCC), to body-centered cubic (BCC), to amorphous structures. Furthermore, the nearest-neighbor distances in the lattices begin to increase above a threshold salt concentration, suggesting that an increase in screening length drives the expansion of the spherical DNA brushes; this anomalous lattice expansion is coincident with the appearance of short-ranged correlations between ions in the bulk solution, as revealed by in situ wide-angle X-ray scattering. These initial results demonstrate how DNA-based nanotechnologies can be made to actuate in response to a very wide range of ionic conditions<b>. </b>To explore the generality of these observations, we investigate assembly induced via the addition of other divalent cations and observe similar general behavior, but distinct sequences of structures, suggesting an ion-specific component to these interactions. The influence of other solution parameters which suggest further avenues for manipulating DNA, such as temperature and dielectric constant, will be discussed. In demonstrating how interactions between DNA continue to evolve past the regime where classical theory predicts electrostatics to become negligible, this work suggests that it is possible to confer additional degrees of functionality based on electrostatic forces to other materials employed at, or far above, biological salt concentrations.