Programing Crystal Growth with DNA Tile Seeds

Nucleation and crystal growth underpin the formation of ordered structures from disordered systems, yet spontaneous nucleation is inherently stochastic and difficult to control. Seeding can introduce preformed nuclei to guide assembly, which offers a strategy to regulate these processes. Here, we investigate seeded nucleation in the two‐dimensional assembly of trimeric macromolecules using programable DNA tiles as a model system. Introducing a single DNA tile as a nucleation seed enabled size‐ and shape‐controlled growth, yielding more homogeneous and reproducible nanoscale assemblies. At moderate seed concentrations, surface coverage increased threefold and crystal uniformity greatly improved. Insufficient seeding failed to impact nucleation, while excessive seeding led to uncontrolled nucleation and higher polydispersity. Across a range of monomer concentrations, seeded assemblies consistently exhibited enhanced coverage and reduced heterogeneity. For more flexible monomers, we designed a specialized seed that effectively regulated nucleation, overcoming challenges in network formation caused by interface flexibility. These results demonstrate how seeded nucleation can transform stochastic growth into predictable assembly, highlighting DNA nanotechnology as a powerful route to engineer highly ordered nanomaterials.