Highlights 2015

About the center

Center for DNA Nanotechnology (CDNA) was established in March 2007 by Kjems, Besenbacher and Gothelf in collaboration with the American researchers Yan and LaBean. In 2012 the center was extended to 2017 by which four scientists, Ferapontova, Dong, Birkedal and Andersen at iNANO were included as senior members, and William Shih at Harvard University became associated with CDNA. The purpose of the research at CDNA is to explore fundamental aspects of DNA as a programmable tool for directing the assembly of molecules and materials into nanoarchitectures and functional structures. The highlights for CDNA in 2015 are described in the following.

 

Controlling the shape of polymers with DNA

Conjugated polymers have several useful applications, owing to their ability to conduct current and emit light. This is e.g. used in organic light emitting diodes (OLEDs) in commercial displays, and TV monitors. One of the visions of the field of molecular electronics, where single molecules constitute the components in electronic circuits, is to use individual conjugated polymers as electronic or optical wires.

In 2015 CDNA researchers published a paper in Nature Nanotechnology that describes the development of a new method to synthesize conjugated polymers containing short DNA strands, extending from each repeat unit along the polymer. To place the polymer, a rectangular DNA origami “board” of dimensions 100×70 nm2 has been formed by self-assembly of hundreds of DNA strands. By coding a specific route on the surface of the DNA board with DNA strands that match the DNA on the polymer, the polymer assembles along the specific path. It allows folding of the polymer in linear and curved paths, as shown for the U-shaped routing of the polymer in Figure 1.

In collaboration with researchers at Harvard University it became possible to route the polymer in 3 dimensions, and image the polymer by the super high resolution microscopy technique called PAINT.

  

Figure 1 Front cover illustration of Nature Nanotechnology showing the immobilisation of a DNA-polymer conjugate on a designed path on DNA origami

 

Novel software tool for single molecule FRET imaging

One of the central techniques for characterizing dynamic processes at the nanoscale is Förster Ressonance Energy Transfer (FRET) and Victoria Birkedal and her group at CDNA are experts in this method. In 2015 they published a paper on the development of a new software tool for single molecule FRET studies in Nature Methods.2 The iSMS software is an interactive toolkit for the comprehensive analysis of smFRET TIRF-microscopy data. The software processes image data almost 20 times faster than current software standards and is used both in parallel to and after data acquisition.

 

An electrochemically controlled dynamic DNA structure

In collaboration between Thom LaBean and two of the Aarhus based CDNA research groups a pH-induced nanomechanical switch incorporated into DNA origami was reported.3 The DNA origami was electronically addressed, demonstrating for the first time the electrochemical read-out of the nanomechanics of DNA origami. This study paves the way for construction of electrode-integrated bioelectronic nanodevices exploiting DNA origami patterns on conductive supports.

Figure  2 Schematic representation of the (A) electrochemical set up used for AFM and electrochemical characterization of DNA origami on basal plane HOPG; (B) origami structure containing the pH-sensitive i-motif in its centre; (C) a typical i-motif quadruplex structure formed in acidic solutions; and (D) possible conformational states of the origami B at (a) pH 8 and (b and d) below pH 5.

 

A DNA-based calculator

In this study two inputs, represented by DNA strands, selects the results for a given calculation from a library of DNA strands and returns the result as a number in a display. This work was performed in collaboration between researchers at Shanghai Institute of Applied Physics and CDNA and it was published in Nature Communications by the end of 2015.4 With further development, it may eventually be used as a diagnostic device, which would use disease-specific nucleic acids as the inputs and retrieve an answer coded in DNA from a pool of possibilities.

 

Figure 3. Illustration of the steps involved in the multiplication, where the two input DNA strands X and Y (e.g. 1 and 2) are converted in to a digital presentation of the result.

 


References

[[1]] Knudsen, J. B.; Liu, L.; Bank Kodal, A. L.; Madsen, M.; Li, Q.; Song, J.; Woehrstein, J. B.; Wickham, S. F.; Strauss, M. T.; Schueder, F.; Vinther, J.; Krissanaprasit, A.; Gudnason, D.; Smith, A. A.; Ogaki, R.; Zelikin, A. N.; Besenbacher, F.; Birkedal, V.; Yin, P.; Shih, W. M.; Jungmann, R.; Dong, M.; Gothelf, K.V. Routing of individual polymers in designed patterns. Nat. Nanotechnol. 2015, 10, 892-898.

 

[2] Preus, S.; Noer, S. L.; Hildebrandt, L. L.; Gudnason, D.; Birkedal, V. iSMS: singlemolecule FRET microscopy software. Nat. Methods. 2015,12, 593-594.

 

[3] Campos, R.; Zhang, S.; Majikes, J. M.; Ferraz, L. C.; LaBean, T. H.; Dong, M.; Ferapontova, E. E. Electronically addressable nanomechanical switching of i-motif DNA origami assembled on basal plane HOPG. Chem. Commun. 2015, 51, 14111-14114.

 

[4] Liu, H.; Wang, J.; Song, S.; Fan, C.; Gothelf, K. V. A DNA-based system for selecting and displaying the combined result of two input variables. Nat. Commun. 2015, 6, 10089.