Optimizing Nanoparticle Assembly via Engineered Fluctuations with Physically-Tethered DNA ‘Bonds’

DNA hybridization has demonstrated to be a powerful tool in the formation of large-scale colloidal assemblies, such as crystals, from nanoparticle building blocks. However, the careful optimization of conditions for assembly and crystallization can be costly and slow when parameters such as DNA-sequence, MW, conjugation density, temperature annealing, and solution conditions are independently modified. Inspired by nature’s reliance on native fluctuations and dynamic physical ‘bonds’, we employed cholesterol-modified single-stranded DNA to physically functionalize nanoparticles engulfed in a lipid bilayer. This configuration enables increased ‘in-plane’ fluctuations of DNA chains around nanoparticle surfaces that allowed for increased lattice (re)-organization at modest temperatures. Moreover, the physical nature of the DNA-lipid bonds enables the formation of assemblies from several different types of nanoparticle building blocks (e.g. silica, gold, clay). To rapidly explore the high-dimensional space involved in such a complex system, high-throughput experimentation (HTE) and robotic automation was adopted throughout this work. First, we used HTE to optimize the formation of lipid bilayers over the surface of nanoparticles using specially formulated lipid mixtures. The formation of the desired structure was subsequently confirmed with high-throughput dynamic light scattering (DLS), SAXS and zeta-potential measurements. Electrostatic forces (via ionic strength), relative concentrations (DNA to particle) and the DNA-sequence were subsequently optimized to maximize the desired formation of specific crystalline structures while minimizing any non-specific aggregation leading to increased disorder. A DNA ‘linker’ molecule that is complementary to particle-tethered DNA on each end was used to induce controlled hybridization and to form DNA-guided nanoparticle assemblies. We explore the effect of fluctuations by comparing the extent of organization in nanoparticles functionalized by saturated and unsaturated lipid bilayers leading to different extents of lateral fluctuations. Finally, we discuss and explore the organization of particles of different chemistry, size, and/or shape to demonstrate the general principles at play in the science of synthesis for such types of colloidal assemblies.