Presenter
William Shih, Harvard University
William is overseeing an effort to apply Synthetic Biology approaches to the development of self-assembling DNA nanostructures and devices for use in biomedical applications. In addition to carrying genetic information, DNA is increasingly being explored for its use as a building material. This new process is called DNA origami because a long strand of DNA can be programmed to fold in on itself to create specific shapes, much as a single sheet of paper is folded to create a variety of …
Fully addressable microstructures self-assembled from crisscrossed DNA-origami slats
Shih’s lab is using DNA origami to construct fully addressable, programmable meshes.
They start with meta-DNA, which is DNA coiled up into structural slats which also contain small nodes poking out at regular intervals made up of specific DNA sequences. These nodes act as programmable attachment points. Slats are assembled into large mesh structures, and the assembly is controlled by requiring multiple binding sites for stability. By doing this, they can use high temperature to prevent a few DNA slats from randomly binding to each other. Seed structures are sown into the mix to initiate binding, overcoming the activation energy barrier.
Slats assemble into lattices, which then grow into sheets and eventually large 1000 slat cloths can be fabricated. Shih has demonstrated fully programmable assemblies capable of complex patterning with applications for nanoscale circuits.
Presentation Slides
- Prototyping multi-micron crisscross structures from combinatorially assembled DNA-origami slats
- DNA has been used to assemble scaffolds in what is known as DNA origami.
Shih’s work focuses on ultrasensitive diagnostics and scaleable fabrication of microscale shapes with nanoscale features.
An example of micrometer DNA arrays, unfortunately the yield drops off as the structures grow in size
Background research on meta-DNA structures – large structures made out of DNA that still behave like DNA but at a different scale.
Meta-DNA assembled into large slats with nodes of DNA used for attachment purposes.
The DNA slats grow by attaching to multiple docking nodes at the same time. 8 bonds are required for stable binding, so at a specific temperature random binding is prevented for all slats except for at the next 8-bond location. Preventing small microstructure assemblies is important for the construction of large, complex, programmed structures.
A seed scaffold can reduce the activation energy and kickstart the process, creating an initial 8-bond location for the slats to begin scaffold construction.
The scaffold is able to grow in a controlled fashion indefinitely.
Electron micrograph data of the structures mentioned so far.
The structures are able to bend and flex.
Another layer of slats was added to stabilize the structure.
The project increased the density of slats from 8×8 to 16×16.
DNA slat structures can be grown to about the same size as organelles such as flagella.
The slats are completely addressable and programmable, so intricate repeating patterns can be created.
Different growth patterns are being used to build out large slat structures. 2D sheets approaching the size of a human cell can be constructed using these techniques. These structures have repeating patterns – in the future, the goal is to have large cell-sized structures with no repeats that are uniquely addressable over their entire surface. The implication here is that these structures could be used to create self-assembling nanoelectronic circuitry in either 2d or 3d.
Examples of programmable patterns in these meta-DNA meshes.
Building fully addressable slats the size of cells.
Most structures go to full completion and are completely seed dependent. The yields for these large structures are extremely high compared to other production methods of DNA origami.
Scaling up the size of DNA structures to roughly ~1000 slats. Much larger than e. coli cells. The largest structures currently have a yield of around 22%.
Scaling up the size of DNA structures to roughly ~1000 slats. Much larger than e. coli cells. The largest structures currently have a yield of around 22%.
Examples of large fully programmable DNA origami sheets.
A summary of the various scales of DNA origami construction explored so far.
These strands are relatively cheap – for a few thousand dollars you can make any slat desired.
Seed dependent construction and robust, rapid, error free growth are they key features of this production process.
Another project in the works – a programmable nanoscale 3d printer.
- Acknowledgements
Seminar summary by Aaron King.
