Beyond Patchy Particles for DNA Superlattice Design

DNA is a molecule with a large engineering potential due to its designable interactions. In the past decade, nanoscale building blocks assembled from DNA have been synthesized through 'DNA-origami' methods. These building blocks have complementary 'patchy' interactions that can be engineered to assemble a variety of superlattices. However, the hierarchical assembly of DNA origami systems has been mostly limited to simple single origami building block assemblies with short-range patch-to-patch attractions. To unlock the full superlattice design space, we seek to combine multiple DNA origami building blocks and predict their co-assembly. In this work, we model the self-assembly of DNA origami 'nanocages' (wireframe polyhedra) self-assembled with complementary double-stranded DNA linkers. The nanocages are linked with double-stranded DNA containing 'sticky' ends complementary to DNA strands on the vertices of the nanocages. Using molecular dynamics simulations implemented with HOOMD-Blue, we show how small changes in the DNA linker-origami interactions can lead to surprising changes in the crystal structures observed in simulation and experiment. Our simulations elucidate that differences in linker binding preferences drive the observed differences in crystal structure thus allowing the assembly of structures inaccessible to the patchy particle paradigm. This combined simulation and experimental work pave the way for future efforts beyond local patch-patch interactions.