Vetturini, A. J.; Cagan, J.; Taylor, R. E.

DNA origami offers a route to engineering architected metamaterials with sub-nanometer precision by linking nanoscale building blocks into micron-scale assemblies. However, automated design spaces are currently limited to fixed DNA origami motifs, restricting the ability to readily tune a mass-efficient nanostructure stiffness. Here, we introduce a fully automated design paradigm that converts prescribed vertices, edges, and cross-section specifications directly into manufacturable, nucleotide-level models. To demonstrate robustness, three structurally distinct nanostructures are realized under a shared experimental protocol. Further, this paradigm enables the deterministic assembly of hollowframe building blocks into micron-scale architectures, including traditional and auxetic reentrant honeycomb lattices. More broadly, this work establishes a novel design abstraction for stiffness-tunable DNA origami nanostructures that can be rapidly translated into architected metamaterials with distinct functional responses.