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Scaffolded Wireframes

DNA scaffolded wireframes are a technique where a long ssDNA scaffold (typically identical to that of the helical bundle DNA nanostructures) is folded into geometric shapes resembling a mesh. As opposed to helical bundles where the DNA helices fill a volume, the wireframe origami helices define the vertices and the edge of the structure with a hollow volume. Whether to use wireframe origami or tightly packed helical origami depends on your application as each class has distinct pros and cons. Wireframe origami generally require less scaffold for a given volume or area, making them more materially efficient. They typically have higher stability in low cationic environments due to their reduced DNA density1. They are often less rigid structurally since the helices are not packed together. Finally, they have different interactions with cellular systems than helically packed origami2. When designing scaffolded wireframes, there are two unique design considerations: scaffold routing and edge architecture.

Scaffold routing for wireframe origami is typically broken down into two categories: A-trail and spanning tree.

  1. Spanning tree routing forms the scaffold into a single Eulerian circuit3.
  2. A-trail routing forms the scaffold into a single unknotted Eulerian circuit4. Depending on your design, A-trail routing may be impossible. If the design is compatible with A-trail routing, A-trail routing enables greater control over local mechanical stiffness4.

Edge architecture is the number of helices that comprise an edge. Each edge of a wireframe can consist of single helices or bundles of multiple helices. Using larger helical bundles typically increases structural fidelity5, but it can reduce the stability in low cationic environments6 and requires larger scaffolds for given volumes.

References

  1. Linko, V. & Keller, A. Stability of DNA Origami Nanostructures in Physiological Media: The Role of Molecular Interactions. Small 19, 2301935 (2023).
  2. Wang, Y. et al. DNA Origami Penetration in Cell Spheroid Tissue Models is Enhanced by Wireframe Design. Advanced Materials 33, 2008457 (2021).
  3. Designer nanoscale DNA assemblies programmed from the top down. Science, https://www.science.org/doi/10.1126/science.aaf4388.
  4. Lolaico, M., Blokhuizen, S., Shen, B., Wang, Y. & Högberg, B. Computer-Aided Design of A-Trail Routed Wireframe DNA Nanostructures with Square Lattice Edges. ACS Nano 17, 6565–6574 (2023).
  5. Jun, H., Wang, X., Bricker, W. P. & Bathe, M. Automated sequence design of 2D wireframe DNA origami with honeycomb edges. Nat Commun 10, 5419 (2019).
  6. Wamhoff, E.-C. et al. Controlling Nuclease Degradation of Wireframe DNA Origami with Minor Groove Binders. ACS Nano 16, 8954–8966 (2022).
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