Assembly of Small Silica Nanoparticles using Lipid-Tethered DNA ‘Bonds’

Single-stranded DNA molecules modified with cholesterol functional groups are physically tethered to silica nanoparticles (Diameter 25 nm) that are encapsulated in a lipid bilayer. This enhances the lateral mobility of the DNA molecules across the nanoparticle surface and enables nonspecific bonding, eliminating the need for specialized surface chemistries (such as silane or thiol ligands). To induce assembly, double-stranded DNA ‘bridge’ molecules are then added with complementary nucleotides to the DNA ‘anchor’ molecules that are physically tethered to the lipids on the surface of the particles. Assembly is observed to occur at room temperature and without the need for temperature annealing. The lateral mobility of DNA on f luid-supported nanoparticles introduces an added degree of freedom that enables the particles to adjust their positions relative to one another, which could be advantageous for the assembly process. Using automated liquid handling tools, assemblies are created in high throughput and rapidly characterized using SAXS. It is determined that the relative concentration of DNA-to-silica and the ionic strength of the solution are important parameters that affect the resulting assembly. Analysis of SAXS data is performed using coarse-grained particle dynamics simulations as a function of the interparticle potential. The results support the spontaneous formation of semi-crystalline particle assemblies by particle condensation, where the interparticle distance is tuned by the sequence of the DNA ‘bridge’ used to link the particles. Crystallinity analysis performed on the resulting simulations, optimized to match SAXS observations, suggest that particle clusters display increased crystallinity in the center of the clusters, but their maximum size remains relatively small (100’s of nm) before settling occurs, which limits the extent of crystallization.