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DNA Origami 68

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."
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DNA Origami

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  • by Anonymous Coward on Sunday March 19, 2006 @11:45PM (#14954777)
    (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
    • Thank you. Very imformative.

      Can you (or anyone) describe what the 'staples' referred to are? It's kind of suprising to hear materials cost as important in the building of nanostructures.

      • I know that it's a little late in the day, but since I didn't see anybody mention the costs involved - the short answer is thousands of dollars.

        The cost of (buying) DNA varies dramatically depending on the length and the purity of a sample, largely because DNA samples of different length are produced by different methods. The cost purification can also add up to more than that of the production. This is one of the reasons why the Nature article specifically mentions common assumptions about the requirement

  • by CrazyJim1 ( 809850 ) on Sunday March 19, 2006 @11:45PM (#14954778) Journal
    I can create a dog out of DNA!
  • by cagle_.25 ( 715952 ) on Sunday March 19, 2006 @11:46PM (#14954782) Journal
    And I'm not a biologist, so don't kill me.

    1. How does the template interact with the DNA to cause self-assembly in the desired pattern?
    2. If I throw RNA in with the object, can the structure reproduce?
    3. Since these are all based on a single gene, they all code for the same protein, right?
    4. How could these structures be used for molecular computing? (the article hints at it; I want details).

    Responses starting with IAABiochemist are encouraged...
    • by Anonymous Coward on Monday March 20, 2006 @12:37AM (#14954906)
      IANA biochemist, but I am a biomedical engineer (in 2 months) and I might be able to shed a little light on the subject.

      1. How does the template interact with the DNA to cause self-assembly in the desired pattern?

      I'm not sure exactly what you mean by template, but essentially what is mixed in solution is one very long strand of DNA and many very small fragments (staples). DNA has 4 bases (A, G, T, C) that bind specifically in AT and GC pairs. When bases are combined into strands they have complementary sequences that will preferentially bind to them, such as AGTT binding to TCAA. In this technique the staples bind to the long strand in such a way as to make it fold a specific way, causing it to automatically assume the desired shape. I didn't read the actual Nature article, but it seems likely that the staples serve to stabilize long portions and force 180 degree turns at the necessary locations on the long DNA strand.

      2. If I throw RNA in with the object, can the structure reproduce?

      No. Look at DNA replication on wikipedia; RNA doesn't really have much to do with replication.

      3. Since these are all based on a single gene, they all code for the same protein, right?

      No. These are not based on genes. These are arbitrary sequences of DNA designed and produced synthetically. They do not code for proteins.

      4. How could these structures be used for molecular computing? (the article hints at it; I want details).

      If we can create any arbitrary 2D structure with 6 nm resolution, this is a major leap over conventional lithography. This means that a 2D design could be made using DNA and then used as a guide for carbon nanotubes or some other technology, vastly improving resolution.
      • The AC (parent) is informative. Mod him up.

        1. "I didn't read the actual Nature article, but it seems likely that the staples serve to stabilize long portions and force 180 degree turns at the necessary locations on the long DNA strand." I've skimmed the article (hopefully, the next comment will be by someone who's actually read the article), and, IIUC, the staples reduce the complexity of knowing how the DNA will fold (wrt secondary structure). Other approaches use superclean strands. This one simply adds t
      • So, is this the Assembler Breakthrough?

        I do hope so.

    • by caenorhabditas ( 914198 ) on Monday March 20, 2006 @03:22AM (#14955312)
      Not a biochemist, but a biology student. Hopefully my answers can help....

      1. How does the template interact with the DNA to cause self-assembly in the desired pattern?

      The thing to understand is that the template is the DNA. DNA binds to other DNA rather specifically, with the A's binding to the T's and the C's binding to the G's. Normally, there's two strands, with one strand containing the binding partners of the other strand. However, in this case, there'll be only one long strand and a bunch of other "staples". The long strand will bind to itself and also the "staples" to form this structure. The self-assembly is induced because it's energetically favorable - the A's "want" to pair with T's, etc. When DNA is heated to around the boiling point of water, however, all of these hydrogen bonds between strands are broken (but, importantly, the strands themselves remain intact). So now a bunch of single-stranded DNA is floating around, but when it's cooled, it assembles into structures. Normally, two DNA strands that are complemenatry would anneal, but in this case, the scientist designs the strand to bind to itself instead. Because it binds to itself in specific places, it forms a predictable structure. In this case, the scientist also used little bits of additional DNA to hold the structure together.

      RNA often forms itself into this sort of secondary structure in nature, but that's typically boring stem-loop structures. In this case, the scientist takes our existing knowledge of nucleotide secondary structure and tried to make his own more interesting secondary structure, to great success.

      2. If I throw RNA in with the object, can the structure reproduce?

      Sadly, it's not as simple as "throwing RNA in there", there needs to be certain enzymes and also the complementary strands of all the DNA in order to work properly. However, it is likely that with the correct mix of enzymes, DNA primers, etc that these things could reproduce themselves, although they'd have to be reassmbled afterwards. I don't think they can replicate themselves in their assembled form.

      3. Since these are all based on a single gene, they all code for the same protein, right?

      I must've missed the part about these coding for genes at all. DNA doesn't have to code for any genes, it can be just DNA that sits around and assembles itself into structures, which I think is what this is.

      4. How could these structures be used for molecular computing?

      Unfortunately, I don't know much about molecular computing, but DNA is a small, predictable, availible substance that we are rapdily getting better at manipulating. Because of this, it's probably the best bet for near-future nanotech, possibly including molecular computing.

      If you are on a university or library connection, you can probably check out the main scientific article here [], which has lots of cool figures and is probably a lot more informative than what I've said. If you're not at a place that can access it, you can find the publication itself anywhere that gets Nature (probably your public library and almost certainly your nearby university). It'd be in the 16 March 2006 issue.
  • by NthDegree256 ( 219656 ) on Sunday March 19, 2006 @11:54PM (#14954798)
    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."
  • by FlyByPC ( 841016 ) on Sunday March 19, 2006 @11:55PM (#14954799) Homepage
    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.
  • Will the future of geek culture be like this? Instead of bored microelectrical engineers making silicon art [], will DNA nano-engineers be making DNA art? :)
  • Two other links. (Score:4, Informative)

    by Stephen Samuel ( 106962 ) <> on Monday March 20, 2006 @12:11AM (#14954838) Homepage Journal
    He also has some earlier work on programming DNA to deposit in the pattern of a Sierpinski triangle [] (fractal)

    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).

  • is it just me, or... (Score:3, Interesting)

    by Khyber ( 864651 ) <> on Monday March 20, 2006 @12:42AM (#14954914) Homepage Journal
    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!
  • If DNA twists... is it 3D or 2D? I'm confused. At what point in 'nano-speak' does something go from 2D to 3D? Okay, molecules on a plane -- 2D. Molecules by themselves -- 3D. It all sounds so... jargoned. Real Life! Now in 3D!!!
    • Everything is 3d, but when one or more dimensions are too small in comparison to the others it is easier to assume that the object has less dimensions. A piece of paper has two large dimensions but one of those is simply too small to account. A DNA, rope, string, and even a heavy chain that holds a ship in place have two dimensions that are much smaller then the other so it is aesier to model them as having only one dimension.

      Those 'drawings' folds the dna in a similar, but not the same, way that you can we
      • Maybe you missed the sarcasm. I am actually working on the problem of protein folding by solving Ramsey problems in Colored-Graph Theory. Look it up. Thanks for caring enough for the explaination though. It was very nice. Thanks.
  • by Anonymous Coward
    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 []
  • Nice work (Score:4, Insightful)

    by Compuser ( 14899 ) on Monday March 20, 2006 @01:55AM (#14955108)
    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.
  • Why is there no image gallery of this stuff? I need new desktop wallpaper!
  • And we are just finding ways to write code for it. The Matrix of the future is right here, under our feet.

    Computational Chemistry will not mean computer simulations of drugs, but the ability to write software in physical hardware, complex chemical structures (DNA) providing a processing capability that will enable us to create physical structures out of software.

    Software that processes and generated a physical form for itself.

    Just when you swallow a red pill labelled 'windows artery' just remember, viruses
    • I was stopped dead by this thought:-

      "that next slice of cake you eat could induce and orgasm."

      And my first thought was "I think I'll stay with girls. They've been inducing orgasms since time began - inherited talent. Further, you can't induce an orgasm in a slice of cake (much less multiple occurrences of the same thing). The family that stays together ..... But then I noticed that your post said

      "could induce and orgasm"

      And we're talking about processors here !

      Aside from contemplation of the possibl

  • by citanon ( 579906 ) on Monday March 20, 2006 @04:56AM (#14955520)

    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.

  • The article mentions that, basically, you can use this technique to create arbitrary 2D shapes out of 6nm pixels.

    10,000,000nm per cm.
    Divide by 6, gives you 1,666,666 pixels (rounding down) per cm.
    Squared gives you 2,777,777,777,776 pixels per cm^2.
    Divide by 8 bits per byte gives you 347,222,222,222 bytes per cm^2.

    Now, this isn't quite accurate, because you can't have disjoint groups. However, there are ways around that: You could create two contiguous groups which XOR to create the data array, giving you 1
    • This technique may have implications for storage (and implications for all of nanotechnology) but it's not directly usable as storage:

      There's a long delay from binary file to programmed DNA while the staple strands are readied. It's read-only. It gets harder, less efficient and more error-prone as you scale it to larger arrays. DNA can be destroyed by all sorts of chemical reactions. Maybe it could somehow be used for bulk reproduction of the same data - like printing CDs today, but I predict that we'll f

    • If you were using DNA for storage, why not use the sequence itself? DNA is fragile however, so some form of enzymic error correction would be needed. This implies a constant source of ATP, GTP, CTP, and TTP.
  • And tommorow they'll be learning how to make a Christmas Tree with Stem Cells! Woot!

    Oh one more thing... you know what this means right? Many years down the road, we will all have our own living mini-pacman..... :D
  • This article immediately reminded me of research on how to control DNA remotely using radio waves [] I read about a few years ago. Adding gold nanoparticles [] to the "DNA staples" of the current work should allow the creation of I/O devices to get from our human scale to this nanoscale to build true supercomputers.
  • Okay...not real versed on DNA, RNA, etc, but...

    Is there a risk that changing things around like this, runs the risk of forming some form of virus that could be quite deadly if not handled properly..

    • As much risk as in accidentally creating an evil super robot by throwing a load of old motherboards in a washing machine and putting it on spin cycle.

      Don't listen to Michael Crichton (or Prince Charles for that matter): there is no grey goo.

Adding manpower to a late software project makes it later. -- F. Brooks, "The Mythical Man-Month"