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DNA Origami
FleaPlus writes "Caltech scientist Paul Rothemund has developed a new technique for designing and generating self-assembling 2D nanostructures out of DNA. To demonstrate the technique, which is reportedly simple enough that a high-schooler can design with it, Rothemund created patterns like smiley faces, text, and a map of the Americas. The technique might be useful for generating 'nanobreadboard' scaffolds for things like molecular-scale circuitry, protein-based factories, and quantum computers. Rothemund is currently working to extend the technique to 3D nanostructures."
It will be even more exciting when you read it here again in a couple of days.
"Everything you know is wrong. (And stupid.)"
Moderation Totals: Wrong=2, Stupid=3, Total=5.
(I think you need a subscription to see the text of the nature article. I'm hesitant to post the entire thing, but here's the Discussion section, which is IMHO the most interesting part)
The scaffolded self-assembly of DNA strands has been used to create linear structures and proposed as a method for creating arbitrary patterns. But the widespread use of scaffolded self-assembly, and in particular the use of long DNA scaffolds in combination with hundreds of short strands, has been inhibited by several misconceptions: it was assumed that (1) sequences must be optimized20 to avoid secondary structure or undesired binding interactions, (2) strands must be highly purified, and (3) strand concentrations must be precisely equimolar. These three criteria are important for the formation of many DNA nanostructures and yet all three are ignored in the present method. For example, M13mp18 is essentially a natural sequence that has a predicted secondary structure which is more stable (lower in energy) than similar random sequences (Supplementary Note S8). Further, stocks of staples each contained a few per cent truncation products, stock concentrations were measured with at least 10% error, and staples were used successfully at stoichiometries that varied over an order of magnitude.
I suggest that several factors contribute to the success of scaffolded DNA origami (even though the method ignores the normal, careful practices of DNA nanotechnology). These are (1) strand invasion, (2) an excess of staples, (3) cooperative effects and (4) design that intentionally does not rely on binding between staples. Briefly (details are given in Supplementary Note S9), strand invasion may allow correct binding of excess full-length staples to displace unwanted secondary structure, incorrect staples, or grossly truncated staples. Further, each correct addition of a staple organizes the scaffold for subsequent binding of adjacent staples and precludes a large set of undesired secondary structures. Last, because staples are not designed to bind one another, their relative concentrations do not matter.
The method presented here is easy to implement, high yield and relatively inexpensive. Three months of effort went into the design program. In addition, each structure required about one week to design and one week to synthesize (commercially); the mixing and annealing of strands required a few hours. The greatest experimental difficulty was acquiring high-resolution AFM images, typically taking two days per structure. For rigid designs using circular scaffolds (rectangles with patterns, three-hole disks, and sharp triangles), yields of qualitatively well-formed structures were at least 70%. A better understanding of folding will depend on less-destructive imaging and quantification of small ( 15 nm) defects. A possible objection to the routine use of the method is the potential cost of staples; unlike the scaffold, staples cannot be cloned. However, unpurified strands are inexpensive so that the scaffold constitutes 80% of the cost, even when using a 100-fold excess of staples (Supplementary Note S10).
I believe that scaffolded DNA origami can be adapted to create more complex or larger structures. For example, the design of three-dimensional structures should be accessible using a straightforward adaptation of the raster fill method given here. If non-repetitive scaffolds of megabase length can be prepared, micrometre-size origami with 20,000 features may be possible. However, the requirement for unique sequence information means that the method cannot be scaled up arbitrarily; whenever structures above a critical size or level of complexity are desired, it will therefore be necessary to combine scaffolded DNA origami with hierarchical self-assembly, algorithmic self-assembly, or top-down fabrication techniques.
An obvious application of patterned DNA origami would be the creation of a 'nanobreadboard', to which diverse components could be added. The attachment of proteins, for example, might allow novel biological
I can create a dog out of DNA!
God spoke to me.
Responses starting with IAABiochemist are encouraged...
Human being (n.): A genetically human, genetically distinct, functioning organism.
I don't think the article on the Discovery Channel website has any more information, but it does have my favorite quote on the subject..."In a typical reaction, he can make about 50 billion Smiley faces. I think this is the most concentrated happiness ever created."
Aren't programs like Folding@Home spending thousands of hours of computer time trying to come up with the proper shape to get drugs to behave in a desired way? Even if there's more to it (which there probably is; biology is far from my strongest subject), the potential for nanomanufacturing sounds very very interesting.
I'm thinking that, if this can be applied to materials of varying conductivity -- or if these materials can be made to replace certain types of DNA -- you could make super-efficient capacitors, photovoltaic cells, etc.
It wouldn't surprise me at all if this ended up being as important a development as the integrated circuit.
Paleotechnologist and connoisseur of pretty shiny things.
His personal page is promising more details by last thursday... (oops). He's out to lunch right now (OK: Supper), so It'll be at least a couple of hours before he gets the update installed (he has been given the heads up).
Free Software: Like love, it grows best when given away.
isn't origami 3-d, not 2-d as the stuff in the submission says? I'm not trying to troll, but I don't see any 2-d origami anywhere on the net. If someone can point me out to 2-D origami, please do, I want to learn!
Still waiting on Serviscope_minor to wake up to fucking reality and realize that Jessica Price isn't going to fuck him.
If you are interested in DNA nanotech, definitely check out the SciAm article by Ned Seeman (the founder of the field). Here are some links to lab pages:
Ned Seeman
William Shih
Eric Winfree
John Reif
I have posted here before being generally critical of many "nano"
results as bullshit or hype, however these results here are for real,
they are a big deal, and they do legitimately go under the moniker of
nanotechnology. One of the few times when the public gets fed stuff as
exciting hype and it is actually exciting underneath.
The Virus strand:
The virus strand serves as the basic starting material for the origami. It's a single stranded, 7000 base long piece of DNA from a virus that attacks bacteria. There are only two reasons the virus strand is used:
1. It is nonrepeating. This is important because every group of 8 bases have a pretty much random sequence of DNA, and can therefore serve as a unique address for a particular position along the length of the virus strand (you get 4^8 = 65536 possible addresses). Thus, in this way, you can address ~1000 distinct points along the length of this viral DNA.
2. It's readily available. Since you can harvest the DNA from the virus, it's cheap to produce. In fact, this strand is commercially available.
DNA staples:
To actually make the virus fold into position, you need several hundred pieces of DNA to serve as staples that stitch together specified positions along the virus strand. Each staple is 32 bases long. Say that you want to stitch together positions A, BC, and D on the virus strand. You then make a staple whose first 8 bases are complementary to those at position A on the virus, whose next 16 bases are complementary to position BC, and whose final 8 bases are complementary to D. The DNA staple will then bind to those positions in solution and staple positions A, BC, and D together into a rigid, tightly packed structure.
You can buy any 32 base long sequences of DNA that you specify from the internet, so getting several hundred distinct strands is no big deal.
Okay, now how do I make a shape?
Think of how you would draw a smiley face with a CRT screen. Your computer has the outlines of the smiley face in memory, and raster-fills the shape. In the case of a virus origami, you first specify the outlines of the shape, then you raster-fill it with the virus strand by running the virus strand side to side from top to bottom. You then figure out all the staples you need to hold your raster-filled shaped together. Finally, you get the sequences, buy them over the internet, throw them together with the virus strand in a solution, and wolah, you get the world's smallest smiley face.
Is this important?
Paul Rothemund may get a trip to Stockholm some day.