Economical and Versatile Subunit Design Principles for Self-Assembled DNA Origami Structures

We describe a modular design approach for creating versatile DNA origami subunits that can target diverse self-assembled structures. The subunit consists of a constant "core module" with variable "bond modules" and "angle modules" added to its exterior, controlling interaction specificity, strength, and structural geometry. The design features flexible joints between subunits, implemented by using single-stranded angle modules, whose mechanical properties and possible conformations are characterized by cryogenic electron microscopy and coarse-grained molecular modeling. We demonstrate the design's versatility through the assembly of structures with different Gaussian curvature, including sheets, spherical shells, and tubes. Our findings suggest that incorporating a judicious amount of flexibility in the bonds provides error tolerance in design and fabrication while maintaining target fidelity. Furthermore, off-target assemblies potentially introduced by flexibility can be counterbalanced by increasing the number of distinct bonds. This approach enables precise targeting of specific structural binding angles across a broad range of configurations by eliminating unfavorable interactions.