(416f) Linker Engineering for DNA Superstructure Design

DNA is a molecule with a large engineering potential due to its well understood, designable interactions. In the past decade, nanoscale building blocks assembled entirely out of DNA have been synthesized through ‘DNA-origami’ methods. These building blocks have simple, complementary interactions that can be engineered to assemble a variety of superlattices. However, the study of DNA origami systems has been mostly limited to simple single origami building block assemblies. To unlock the full potential of the DNA design space to engineer complex superstructures, we seek to combine multiple DNA origami building block shapes 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 DNA origami nanocages are not complementary to each other but are instead linked together with double-stranded DNA containing sticky ends complementary to DNA strands on the vertices of the nanocages. Using coarse grained 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 nanoscale binding preferences drive the observed differences in crystal structure and allow us to engineer crystal structures for multiple linker-mediated DNA origami nanocage assemblies. This combined simulation, experimental work, thereby paves the way for future efforts in engineering final DNA superstructures and DNA lattices that can reconfigure via in-situ modification of nanoscale interactions.