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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."
(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 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."