DNA Nanotechnology: Enabling technologies and applications
Previous and Current Research
Why building with DNA?
In the DNA chemistry group, we are excited about engineering at the nanometer-scale. DNA is not only nature’s preferred information storage molecule, but also the most versatile and programmable material to build artificial nanostructures. DNA nanostructures can be used to arrange functional elements such as proteins, fluorophores or optically active inorganic nanoparticles in 3 dimensions with nanometer precision. The achievable positioning resolution beats any other methods such as lithography. Moreover, trillions of copies of a structure or device can be self-assembled in parallel in a drop of water.
DNA-based plasmonic devices
Nanometer-sized metallic nanoparticles show extraordinary optical properties when irradiated with light. One of these phenomena are ‘plasmons’ (collective oscillations of the conducting electrons in such particles) which can be used to guide and manipulate light below the diffraction limit. We use the power of DNA self-assembly to build and test nanophotonic devices such as plasmonic waveguides for application in optical near-field communication, or for medical diagnostics and therapeutics.
Further reading: ACS Nano (2016).
(see figure 1 below)
Triangulated DNA origami
In the macroscopic world, stiff and material-efficient structures such as construction cranes and high voltage transmission towers are usually built from triangulated wireframe structures. We extended the DNA origami concept to generate a series of triangulated trusses. These provide defined cavities that we seek to fill with functional elements. Moreover, we are determining biophysical properties such as their bending and torsional stiffness.
Further reading: Nano Lett. (2016).
(see figure 2 below)
Enzymatic oligonucleotide production
Synthetic oligonucleotides are the main cost factor for many studies in DNA nanotechnology, genetics and synthetic biology that require thousands of these at high quality. Inexpensive chip-synthesized oligonucleotide libraries can contain hundreds of thousands of distinct sequences, however only at sub-femtomole quantities per strand. We developed a selective oligonucleotide amplification method with a 10-1000-fold cost-reduction compared to synthetic oligonucleotides or competing amplification methods such as PCR. We are currently continuing to improve the method and explore new applications.
Further reading: Nat. Commun. (2015).
Protection of DNA structures
A main drawback of structural DNA nanotechnology is the instability of structures in biological environments. To this end, we developed a protection strategy based on block copolymer micellization which stabilizes DNA structures in biological or low-salt environments.
(see figure 3 below)
Several other multi-disciplinary projects are being followed at the interface of Chemistry, Physics, Biology and Electronics. Examples include mechanistic studies of the rolling circle amplification, imaging of biological tissues or single-molecule biophysics of proteins.
Future Projects and Goals
We will continue to work at the interface of Chemistry, Physics and Biology. Apart from the projects mentioned above, I seek to strengthen the Chemistry branch in the group. For example, chemically modified DNA nanostructures shall be used to mimic protein surfaces. We are also working on new methods to chemically stabilize DNA nanoarchitectures and devices against thermal, chemical and physical degradation and on methods to produce large, hierarchical multi-component DNA nanoarchitectures.
Methodological and Technical Expertise
- DNA nanotechnology (CAD sequence design, assembly, gel imaging)
- Enzymatic reactions
- Chemical bioconjugation
- Organic synthesis, oligonucleotide synthesis
- Inorganic nanoparticle synthesis and functionalization
- High resolution imaging (AFM, TEM, SEM, S-TEM)
Gür, F. N., Schwarz, F. W., Ye, J., Diez, S., Schmidt, T. L.
Toward Self-Assembled Plasmonic Devices: High-Yield Arrangement of Gold Nanoparticles on DNA Origami Templates.
ACS Nano 2016, 10 (5), 5374–5382.
Matthies, M., Agarwal, N. P., Schmidt, T. L.
Design and Synthesis of Triangulated DNA Origami Trusses.
Nano Lett. 2016, 16 (3), 2108–2113.
Schmidt, T. L., Beliveau, B. J., Uca, Y. O., Theilmann, M., Da Cruz, F., Wu, C.-T., Shih, W. M.
Scalable Amplification of Strand Subsets from Chip-Synthesized Oligonucleotide Libraries.
Nat. Commun. 2015, 6, 8634.
Schmidt, T. L., Heckel, A.
Construction of a Structurally Defined Double-Stranded DNA Catenane.
Nano Lett. 2011, 1739–1741.