DNA Origami

DNA origami provided me with the first hint that there might be research worth pursuing outside of physics, which, as a physicist, was a sort of revelation.  The idea behind DNA origami was deceivingly simple, but offered so many interesting questions.  Given our knowledge of DNA, could we use it to make nanostructures?

Most people, at least I like to think that most people, are familiar with DNA’s double helix geometry and that it contains some sequence of four different “units” strung along a sugar-phosphate backbone.  The four units are nucleobases: adenine, guanine, cytosine, and thymine, also referred to as A, G, C, and T.  The bases bind together to form base pairs, A with T and G with C. The binding then connects two strands of DNA to form the double helix (see below).

From http://karimedalla.wordpress.com/2012/11/01/3-3-7-1-dna-structure/

DNA’s functions and forms are very pretty things to consider and I would like to talk about why DNA components form a double helix and how the base pairings work in biological processes and so on, but we’ll stick with the basics for now.  We have four basic units that have preferential binding to one another, all connected by backbone that forms some polymer.  Given this, I’ll ask again: is it possible to fit DNA into other shapes beyond our beloved double helix?

Paul W. K. Rothemund put forth an answer in this paper at Caltech in 2006.  He used a method termed “DNA origami” to fold DNA into various shapes approximately 100 nanometers (think one tenth the width of a human hair) in size.  The method involved one long (~7000 bases) strand of DNA along with many shorter (~32 bases) “staple” strands.  The long strand would fold back and forth along some pattern based on its sequence of bases and the staple strands would help hold the structure together (see below).

From figure 1 of Rothemund, Paul W. K.  (March 16, 2006).  Folding DNA to create nanoscale shapes and patterns.  Nature, 440.  doi:10.1038/nature04586

The DNA still forms the double helix, but the helix itself folds and crosses over and connects with staple strands to form a design.  The variety of possible shapes is large.  For example, see the samples used in the paper shown below:

From figure 2 of Rothemund, Paul W. K.  (March 16, 2006).  Folding DNA to create nanoscale shapes and patterns.  Nature, 440.  doi:10.1038/nature04586

The top two rows are schematics of the design while the bottom two are atomic force microscopy images of the structures themselves.

Not only can we form two dimensional shapes, but we can also make 3d structures as well.  They can have branches or be hollow or or have dynamic parts.  And scientists are developing different methods that will further enlarge the variety of structures we can form!

I was, and am, amazed by the new ideas that such a familiar, ubiquitous molecule inspire.  Something we used to think of as working strictly within cells has applications in drug delivery, imaging, and art.  It’s easy to go overboard and say the possibilities are unlimited.  Given so many applications, it is rather hard to resist the sense of power one might get knowing that one can manipulate DNA to do one’s bidding.  In fact, I might just have found some extra motivation to attend grad school seeing how the title “Professional DNA Whisperer” has a nice sound to it.  Hopefully I won’t get carried away with my new-found power along the way.