Economical and versatile subunit design principles for self-assembled DNA origami structures

Abstract: Self-assembly of nanoscale synthetic subunits is a promising bottom-up strategy for fabrication of functional materials. Here, we introduce a design principle for DNA origami nanoparticles of 50-nm size, exploiting modularity, to make a family of versatile subunits that can target an abundant variety of self-assembled structures. The subunits are based on a core module that remains constant among all the subunits. Variable bond modules and angle modules are added to the exterior of the core to control interaction specificity, strength and structural geometry. A series of subunits with designed bond/angle modules are demonstrated to self-assemble into a rich variety of structures with different Gaussian curvatures, exemplified by sheets, spherical shells, and tubes. The design features flexible joints implemented using single-stranded angle modules between adjacent subunits whose mechanical properties, such as bending elastic moduli, are inferred from cryo-EM. Our findings suggest that incorporating a judicious amount of flexibility in the bond provides error tolerances in design and fabrication while still guaranteeing target fidelity. Lastly, while increasing flexibility could introduce greater variability and potential errors in assembly, these effects can be counterbalanced by increasing the number of distinct bonds, thereby allowing for precise targeting of specific structural binding angles within a broad range of configurations.