DNA origami with... hair?

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Today, I am focusing again on DNA origami! It’s been a while.

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DNA origami with… hair?

In this issue’s paper, the team focused on hairygami: a flat DNA origami structure covered with single-stranded DNA overhangs. These overhangs extend from the surface and interact with other molecules or their environment. But how do these extra strands affect the DNA origami itself? Let’s take a step back to understand.

DNA origami is used to position molecules with nanoscale precision, since we know where each nucleotide is going to be in the final structure. Flat DNA origami especially have been used as a pegboard to assemble proteins, aptamers, peptides, gold nanoparticles, and more. Typically, these additional molecules are attached using single-stranded overhangs that extend from the DNA structure. But in this paper, the authors asked a simple yet intriguing question: do these "hairy" overhangs change the structure, and therefore the function, of the DNA origami?

One challenge is that it’s tough to experimentally capture the conformation of DNA origami in solution. Techniques like AFM and TEM are great, but they require the structures to be on a surface, which doesn’t represent how they behave in liquid environments. And cryo-EM uses averages, which could not represent some of the conformations in solution. So, the team turned to a computational approach with oxDNA, a coarse-grained model that simplifies molecular details but allows faster simulations. They focused on 2D flat DNA sheets and analyzed how single-stranded and double-stranded overhangs affect the structure.

The simulations showed that the addition of overhangs causes the flat DNA origami to bend. The entropy generated by the overhangs is the main culprit for this curvature: overhangs create steric hindrance (spatial crowding), which pushes the nanostructure to bend or curve to minimize interactions between neighboring overhangs. When the structure bends, more space is available for the overhangs, creating a more stable configuration. The team tested different overhang lengths (9nt and 20nt) and found that longer overhangs caused more bending, due to higher entropic pressure. Density also mattered—more overhangs per unit area led to stronger curvature. They also compared single-stranded (ssDNA) and double-stranded (dsDNA) overhangs. Interestingly, dsDNA also caused bending, but to a lesser extent because it’s more rigid than the flexible ssDNA.

And all of this insight was “just” from the computational modeling! But then the team went a step further and designed a clever experiment. They created a flat DNA structure with lateral overhangs that would either connect to other structures if flat, or self-assemble into a nanotube if bent. Using gel electrophoresis and TEM, they showed that the overhangs caused the structure to bend into nanotubes, proving their hypothesis in the lab: super smart!

This is a very interesting paper, and, while it might seem like it focuses on a detail of DNA origami design, this research have repercussion in different areas:

• Biotech and Drug Delivery: The shape of DNA origami could be key in how well it interacts with cells or delivers therapeutic cargo, making this study relevant for designing more efficient drug delivery systems.

• Nanophotonics: DNA origami could be used to precisely arrange optical components at the nanoscale. Controlling the bending behavior opens up new design possibilities for light-responsive devices.

• Biosensing: The structural changes caused by overhangs could be leveraged for biosensing, where the bending of the nanostructure signals the presence of a specific molecule.

There is more in the paper, including a discussion around the effect of the salt concentration and the bending induced by proteins, so go and check it out!

In other news:

• DNA origami bubble blower: We are all children inside, a little bit. That’s probably why this team created a DNA origami "bubble blower", a nanoscale tool that seeds and controls the formation of uniform nanometric liposomes. The bubble blower offers a reusable, efficient solution for creating smaller, consistent liposomes. So, fun and useful!

• Fitting DNA origami into nanopores: This study shows that integrating DNA origami with solid-state nanopores significantly enhances the detection sensitivity of proteins, using holo human serum transferrin as a model. This method offers potential for ultrasensitive biosensing and could improve diagnostics for diseases with low-abundance protein biomarkers. Pretty cool application of DNA origami!

• Making lights with bacteria: Apparently, now you can make LED using bacteria. This study introduces bacteria-based photon down-converting filters for white LEDs, eliminating the need for costly purification. By creating living spheroplasts (a microbial cell with removed cell wall), the researchers achieved long-term stability in polymer films and developed the first bacteria-hybrid LEDs. These devices are cost-effective, reusable, and offer similar stability to purified FPs, marking a new concept in living lighting systems.

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