Computer-Aided Design of A-Trail Routed Wireframe DNA Nanostructures with Square Lattice Edges

In recent years, interest in wireframe DNA origami has increased, with different designs, software, and applications emerging at a fast pace. It is now possible to design a wide variety of shapes by starting with a 2D or 3D mesh and using different scaffold routing strategies. The design choices of the edges in wireframe structures can be important in some applications and have already been shown to influence the interactions between nanostructures and cells. In this work, we increase the alternatives for the design of A-trail routed wireframe DNA structures by using four-helix bundles (4HB). Our approach is based on the incorporation of additional helices to the edges of the wireframe structure to create a 4HB on a square lattice. We first developed the software for the design of these structures, followed by a demonstration of the successful design and folding of a library of structures, and then, finally, we investigated the higher mechanical rigidity of the reinforced structures. In addition, the routing of the scaffold allows us to easily incorporate these reinforced edges together with more flexible, single helix edges, thereby allowing the user to customize the desired stiffness of the structure. We demonstrated the successful folding of this type of hybrid structure and the different stiffnesses of the different parts of the nanostructures using a combination of computational and experimental techniques.

Automated summary

In recent years, there has been a growing interest in wireframe DNA origami, with various designs, software, and applications emerging rapidly. This study focuses on increasing the design options for A-trail routed wireframe DNA structures by incorporating four-helix bundles (4HB). The researchers developed software for designing these structures, successfully demonstrated the design and folding of a library of structures, and investigated the mechanical rigidity of the reinforced structures. The scaffold routing technique allows for the easy incorporation of reinforced edges and flexible single helix edges, enabling customization of the desired structure's stiffness. The successful folding of hybrid structures and the characterization of different stiffness levels using computational and experimental approaches were demonstrated.