DNA Wireframe Revolution: Scaffold-Free Mesh Innovation!

DNA nanotech has made huge steps, from a handful of strands and motifs to complex structures. While the most common technology is DNA origami, today I bring you an advancement for the runner-up: wireframe, scaffold-free assembly!

Today’s paper has a nostalgic feeling for me: DNA nanotech and wireframe structures? Yeah, that’s my PhD right there!

Let’s dive right in.

DNA Meshes, Scaffold-Free

From Origami to Scaffold-Free Structures

DNA nanotech has come a long way.

What started with simple single stranded DNA and manual design has evolved into an entire field. Nowadays, structures are much more complex, and DNA origami is the most common approach to create them. DNA origami uses a long, single stranded DNA (ssDNA) scaffold and a series of short ssDNA staples to create nanostructures.

But this powerful technique comes with limitations:

• The scaffold has fixed length, so there’s a limit to how big the structures can be

• Designing these structures require complex routing of a single strand

• The topology is can be complicated: some shapes don’t work well with a single strand

Scaffold-free DNA nanostructures are a strong alternative. In these structures each strand acts a Lego brick, interacting only with its neighbors. This strategy removes the scaffold completely, and with it the size constraint! In addition, there are less design limitations: no long, circular strand to weave through the design!

But while the possible design freedom is huge, actual implementations have lagged behind. Until now.

BRAIDS: Automated Design of Wireframe Structures

Today’s paper introduces BRAIDS, the first automated pipeline for designing scaffold-free wireframe DNA structures.

Wireframe structures are hollow, mesh-based structures common in computer graphics and architecture. They use the DNA material more efficiently, but are much harder to design! And that’s exactly what BRAIDS solves.

The authors used BRAIDS to create 2D and 3D structures, some of them much larger than DNA origami ones! A cool feature is the use of triangulated faces, to increase the rigidity of these structures, a well-know problem (I have not one, but two papers on this! Shameless plug).

From Mesh to Structure: How BRAIDS Works

Here’s how the pipeline looks.

1. Start with a polygonal mesh.

   Ah, so nostalgic! This is nothing more than a collection of polygonal faces, glued together along the edges to create a shape.

2. Route DNA along the mesh edges.

   BRAIDS turn the edges of the mesh into circular ssDNA, following a clockwise orientation for each face. In this way, each edge ends up with 2 antiparallel DNA strands: perfect to form a DNA double helix!

3. Nick the loops.

   The circular strands are nicked into linear ones, so they can be synthetized. The crossovers between strands at the vertices create a junction that connects different edges.

4. Generate the DNA sequences.

   The geometry is defined and the software generates the DNA sequences to order.

And voilà! Just like that you have your DNA nanostructure. It is much easier than doing it with DNA origami, trust me.

Real-World Results: 2D and 3D Designs

The authors designed a bunch of 2D and 3D structures to see how the system performed, focusing in particular on the scalability: this means big structures!

2D Wireframes

To test scalability, the authors designed flat squares of increasing sizes:

• 220 strands, with 7840 nt

• 494 strands, with 16796 nt

• 874 strands, with a whopping 28716 nt!

For reference, DNA origami structures are generally around 15-16000 nt total.

But they didn’t stop there. They also created 2 complex structures representing Chinese characters, to test the precision of the system. The two structure, 782 and 1212 (!) strands respectively, assembled beautifully, showing fine features even at this complexity and size!

3D Wireframes

The authors also created 3D structures, using 2 types of meshes.

First, they tackled 2 freeform designs, a 23862-nt flask a DNA version of the vessel from the 1966 movie “Fantastic Voyage”! These were complex and irregular designs. After synthesis, some of the features were deformed, and the yield was not great. But it’s honestly impressive that they managed to synthetized them at all!

Second, the team moved to design cubic lattices. Thanks to the more regular design, these had a better yield than the irregular shapes. The authors created lattices of different sizes, up to a whopping 37000 nt! These were bigger than ever before, and more rigid, thanks to the triangulation.

These cubic lattices would make the perfect scaffolds for molecules of any size, like proteins or nanoparticles!

Conclusions and Future Directions

The authors created a modular, scalable and efficient alternative to DNA origami.

BRAIDS allows the creation of 2D and 3D structures, in theory without any scale limitation. There are some challenges, though. The yield of irregular shapes is low, and there is structural variability. The synthesis is also not easy, because annealing protocols and strand composition have to be carefully optimized.

This opens up future work: for example, machine learning could be used for optimization of DNA sequences or of synthesis condition!

This is an exciting paper: DNA origami has plenty of tools for automated designs of wireframe structures, and it was time for scaffold-free to catch up! The lattices are particularly interesting. They are hard to make and scale with DNA origami, and they could be useful for applications in synthetic biology, nanofabrication and biomaterials!

But don’t take my word for it: go and read the paper here!

If you made it this far, thank you! Do you have thoughts on DNA nanotech? Do you have something in mind using these new tech? Reply and let me know!

More Room:

• Locking Your Info in DNA: Information is becoming more and more important into our world, and so are ways to secure it. This study presents a DNA-based cryptographic system using a dynamic, self-calibrating network with an adaptive threshold, improving message decoding accuracy by adjusting to environmental changes. It reduces errors seen in fixed-threshold systems and supports message expansion and DNA sensing through nanoparticle-based amplifiers. A field to watch for sure!

• Tanning DNA Nanostructures: DNA nanostructures also have to worry about UV light (and with summer upon us, it’s a good reminder to put on sunscreen!). This study demonstrates the use of UV-crosslinked DNA nanomaterials for enhanced targeted delivery to cancer cells. By arranging folate ligands with nanoscale precision and rigidifying the structures, the researchers improved stability, cellular uptake, and gene silencing efficiency in folate receptor–positive cells. Cool work!

• Pulling on DNA Origami: Another love from my PhD: mixing DNA origami with force generation. In this study, DNA origami meets optical tweezers and computational modeling to reveal hidden intermediates in protein folding! Using calerythrin as a model, the rigid DNA origami handles enabled the detection of a previously unseen folding intermediate and clarified the protein’s hierarchical folding pathway. Comparison with AlphaFold predictions across calcium-binding proteins provided structural insights into these intermediates. Promising research for sure!

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