Sunday, 13 September 2015

Shameless self-promotion: Engineering self-assembly pathways

Over the last two weeks we've finally managed to get our paper on self-assembly pathways published in Nature ("we" includes the Turberfield and Kwiatkowska groups in Oxford). In the paper, we look at a type of nanostructure called DNA origami.  DNA origami is a wonderfully versatile approach to create structures with a typical size of a few hundred nanometres, but with the possibility of adding details within a precision of a few nanometres. For real "wow-factor", just type "DNA origami" into Google image search.

The principle is remarkably simple. We start with one long DNA strand (see the pink and green object in the above picture) - this is known as the "scaffold". We then introduce a number of much shorter strands called "staples" (blue in the above picture). These staples are designed to stick to two (or more) specific parts of the scaffold very strongly, bringing them together and folding the scaffold into a complicated shape.

A number of people have made incredibly sophisticated structures, in both 2d and 3d, with this technique. However, we were more interested in understanding how the structures formed, and whether we could design them to form more efficiently. We therefore started with a simple rectangular design. Our unusual step was then to double the scaffold, so that it contained two identical halves (pink and green sections in the picture above). This meant that each staple could stick in a number of configurations, because each binding site appeared twice on the double scaffold.

Despite this, most scaffolds folded into one of a small number of distinct shapes, which looked like two rectangles lying side-by-side: example microscope images are shown in (b) and (c) above. We saw that certain shapes were more favourable than others. More interestingly, we were able to change which shapes were most common by making small adjustments to the staple strands. We were able to predict the changes using a theoretical model that we discuss in an even newer paper. The success of our model gives us some hope that we might be able to design origami rationally to improve the reliability of self-assembly.

From a general perspective of  using molecules to achieve complex tasks, the most interesting thing is that we were able to manipulate self-assembly outcomes by interfering with the folding pathway, rather than the stability of the final structures. The obvious way to force a system to assemble into a certain shape is to design your system so that your chosen structure has by far the lowest energy (technically, free energy) of all configurations. However, the alterations we made to staples should have had almost no effect on the relative energies of the different configurations. Instead, our modifications changed the order in which staples attached to the scaffold - and this order is crucial, as the early staples shape the scaffold, determining which of the possible structures will eventually form.

1 comment:

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