Conference on DNA Computing Liveblog 9

Kurt Gothelf showed how DNA can be used to assemble polymers. I usually think of polymerization reactions as being very random. I thought it was interesting that he can define a path across the surface of a DNA origami tile to make a directed polymer chain. The shape and structure are both controlled. These polymers also bind carbon nanotubes, so now you can put carbon nanotuves along defined paths? That sounds promising.

Tim Liedl talked about engineering metamaterials with DNA. Metamaterials have behavior that depends on their structure rather than their composition. Gold nanoparticles are very different than solid gold. They are arranging the gold/metal nanoparticles by using DNA. I lost the thread of the novelty of this material. I do remember when this group published a paper using gold nanoparticle-decorated DNA to control the chirality and optical activity of structures. They could make the little spiral gold structures rotate polarized light left or right depending on how they assembled it.

William Shih showed how to purify origami nanostructures with density gradient centrifugation. That is nice because there is no gel or ethidium bromide (dye) to contaminate the DNA. One surprising result was that mechanical strain can help things fold. Maybe that is energetic due to farther apart crossovers, or maybe (my speculation) the effect is kinetic by making things less stable but faster to invade by staple strands. The talk was very technical on how to purify and analyze which I found interesting. One of the big questions is how to direct the folding pathway as well as the thermodynamic minimum.

John Chaput is from ASU and talked about other DNA-mimic polymers. Evidently TNA (threose) works with therminator polymerase? Alas, TNA are not really hydrophobic. They are able to make aptamers. Alternative (like GNA) backbones can relatively easily be made right-handed and left-handed. The thermodynamic forces are stronger for intra-strand base-base interactions relative to DNA so GNA-GNA hybridization is stronger. The GNA helix is very different and won’t recognize DNA. For the same reason, it can not be recognized by a DNA polymerase.

Hanadi Sleiman talked about orthogonal interactions and temporal growth. For longer term biomedical applications, DNA-based nanotechnology presents a big problem: we can not make tons or even kilograms of these structures. There are also potentially some nasty problems with increasing numbers of random sequences (staples) that might have biological effects. Potentially, it is possible to make a ssDNA origami. But it’s not as addressable; it’s repetitive inherently. And it is still not clear how it can be scaled.

She also talked a little about electrochemistry of DNA. Interestingly, charge transport only occurs through fully-paired DNA. Where is the electric current going? It goes to gold particle, then where? DNA can capture a particle. I remember this work from FNANO. She builds a cage of ssDNA arms that can trap a gold nanoparticle guest. The host can be rigidified with additional hybridized DNA and the guest can be trapped. They are hoping for size-matched host-guest interactions.

Peng Yin talked about the DNA bricks, which were presented earlier but which were amazing. Then he talked about brick crystals. Brick structures can be made into unit cells of gigadalton objects. Bricks can be “voxels” control location. Can we control reactions to occur within regions of the DNA “brick building?”

The Yin lab is encoding bits into DNA and controlling matter. That’s beautiful, but how can it be useful? One way might be by integrating with lithography. The Yin lab did make a silicon dioxide conforming shell. They also deposit DNA, metalize it, and use it as a mask for etching grapheme. How to manipulate grapheme is a big and important problem. Another route to nanofabrication from DNA inorganic structures is to grow silver inside the a DNA origami box. This seems more like something for nanotech in the classical, “Drexlerian” sense.

Robust, specific, DNA or RNA probes can be generated with specific delta-G that is optimal for discrimination of even single base changes. Optimized toehold probes may be better than molecular beacons. Toehold probes’ interactions with structures can be well-characterized. This also relates back to the 3D reconstruction and visualization with DNA-PAINT because it enables “programmable blinking.” The controlled, and programmed blinking enables resolution beyond the normal diffraction limit.

RNA structures in living cells: they also made a toehold ribiregulator. A gene is regulated by the riboregulator which is actuated by an RNA trigger. It seems that you can do toehold switch in a living cell. Induce RNA-1 get Protein-2. Is RNA1 introduced or induced? Maybe either.

Dongsheng Liu showed off nanomotors and the nanopore. The binding affinity can be driven by motors (strand displacement driven, I thought). Hydrogels can be assembled with DNA. This is really relevant to my interests. These hydrogels can be triggered by pH to assemble or dissemble because different DNA sequences are pH sensitive. Under some conditions, the DNA molecules interlock but other conditions allow the DNA connections to dissolve. The hydrogel traps nanoparticles but not small molecules. I wonder what DNA coated particles would do inside this kind of gel.

They are working toward applications in tissue engineering: the gel is transparent to small molecules even though big particles (like cells) are trapped. The material properties can be designed. The gel’s mechanical strength changes on pressure/shear. So maybe it is injectable? It’s a shear thinning material. They are also self-healing. They mix into one another to form a stable gel. That sounds like superdiffusion by coupled motion of the polymer chains. This was the only other tissue engineering talk, so that’s exciting to me that there is more interest than just mine within this community.