Today and tomorrow, we're reporting on presentations at an important conference on Productive Nanosystems: Launching the Technology Roadmap. Chris Phoenix is providing live blog coverage for us...
Next talk: William Shih, "From Structural DNA Nanotechnology to NMR Membrane Protein Structure"
We'll hear two stories. First, nanotubes built out of DNA to solve the atomic structure of membrane proteins. Second, using DNA nanotubes to assemble wire-frame cages quite a bit larger than cages built in the past.
Holy grail for the DNA nanotechnology field (founder Ned Seeman's original goal) is to make a hollow crystal of DNA, then bind the target protein into the hollows. But this requires very precise spatial ordering.
(You want proteins arranged in a crystal, because then when you shoot X-rays through them, you can tell the structure. Shih just said that you can use NMR to determine structure, and it doesn't need such precise placement.)
There are (at least) three classes of proteins they're interested in: adrenaline receptors, ion channels, and (I didn't catch it). Membrane proteins are very important as drug targets, but very hard to analyze. It's hard to purify them in the first place, and then to get them to line up is another level of difficulty.
Membrane proteins have lots of methyl groups, which confuse the NMR signal. But you can also determine angular information--if you can make the proteins line up. You want 0.1% of the proteins to be aligned. So you mix them with a dilute liquid crystal. But membrane proteins are stabilized with detergent, which is incompatible with known liquid crystals. So... build a liquid crystal-type thing out of DNA! (A long thin filament.)
Just designing DNA strands that assemble into filaments isn't enough, because you'll get a distribution of lengths. So... use Rothemund's DNA Staple technology. There's enough DNA in the standard strand to build a 400-nm length of six helices. They wanted longer, so built two of these things designed to stick in pairs.
And... they form a dilute liquid crystal. (It exhibits birefringence.) And when mixed with a known protein, they found the signal they expected. Good signal-to-noise ratio. Now they're looking at proteins with unknown structure. This extends the range of NMR from 15(?) to 40 kilodaltons.
Now, the second story: Building arbitrary DNA structures. Of large size: the field has been stuck at 25 nm geometric figures since about 2004. Icosahedron - 30 struts: 100 nm wide. Build it out of three double-triangles. And... it works! (Though there's some squishiness.) It looks symmetric, but each strut has a different sequence. There's about 500 different staples: that's 500 different places to hang some protein.
My conclusion: Nice that they can build big engineered structures. May be useful for research and maybe even for construction of moveable-part nanomachines.
Chris Phoenix
Tags: nanotechnology nanotech nano science technology ethics weblog blog
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