Universal 3D Nanoscale Assembly with DNA Polycubes

We present the DNA polycube platform, where cubed-shaped DNA nanostructures are used as building blocks that self-assemble into larger arbitrary 3D shapes. We use a multiscale simulation platform combined with constrained optimization that solves the inverse design problem by identifying the smallest number of distinct blocks that are required to assemble a target 3D shape and avoid misassembled states. We demonstrate this approach with the design and experimental realization of finite-size as well as lattice structures, including complex shapes such as a fractal Menger Cube. We further introduce out-of-equilibrium rearrangement of structures, where assembled DNA polycubes can be reconfigured by introducing a set of invader cubes that displace the ones in the structure. We demonstrate the suitability of our platform for positioning different functional groups in 3D by attaching functional cargoes to the building blocks and creating a 3D carbon nanotube junction, thus opening pathways to precise 3D nanofabrication by self-assembly.