CENTER FOR DNA NANOTECHNOLOGY 2015 -...

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CENTER FOR DNA NANOTECHNOLOGY 2015 - HIGHLIGHTS 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 nm 2 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.

Transcript of CENTER FOR DNA NANOTECHNOLOGY 2015 -...

CENTER FOR DNA NANOTECHNOLOGY 2015 - HIGHLIGHTS

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.

CENTER FOR DNA NANOTEKNOLOGI 2015 - HØJDEPUNKTER

Om centret Center for DNA Nanoteknologi (CDNA) blev etableret i marts 2007 af Kjems, Besenbacher og Gothelf i samarbejde med de amerikanske forskere Yan og LaBean. I 2012 blev centret forlænget til 2017 og udvidet med fire forskere, Ferapontova, Dong, Birkedal og Andersen ved iNANO samt William Shih på Harvard University. Formålet med forskningen ved CDNA er at udforske fundamentale aspekter af DNA som et programmerbart materiale, der kan anvendes til at dirigere selvorganisering af molekyler og materialer til nanostrukturer og funktionelle nanosystemer. Højdepunkterne for centrets forskning i 2015 beskrives i det følgende. Foldning af konjugerede polymerer med DNA Konjugerede polymerer har mange værdifulde egenskaber pga. deres evne til at lede strøm og udsende lys. Dette bruges f.eks. i organiske lysdioder (OLED) displays, og i tv-skærme. En af visionerne indenfor området molekylær elektronik, hvor enkelte molekyler udgør komponenter i elektroniske kredsløb, er at bruge individuelle konjugerede polymerer som elektroniske eller optiske ledninger. I 2015 offentliggjorde forskere fra CDNA en artikel i Nature Nanotechnology, der beskriver udviklingen af en ny metode til at syntetisere konjugerede polymerer med korte DNA-strenge, der strækker sig ud fra hver gentagelsesenhed langs polymeren.1 For at kontrollere formen af polymeren, anvendes DNA origami, hvilket er en flad 100 × 70 nm2 nanostruktur dannet ved selv-samling af hundredvis af DNA-strenge. Ved kodning af en bestemt rute på overfladen af DNA-origamistrukturen med DNA-strenge, der matcher DNA'et konjugeret til polymeren, immobiliseres polymeren langs den angivne rute (Figur 1). Dette tillader foldning af polymeren i lineære og buede former, som vist for den U-formede polymer i Figur 1. I samarbejde med forskere fra Harvard Universitet var det også muligt at folde polymeren i 3 dimensioner, og dette blev visualiseret ved en super-højt-opløsnings-mikroskopiteknik kaldet PAINT.

Figur 1 Forside fra Nature Nanotechnology der viser immobilisering af et DNA-polymer-konjugat på en designet rute på DNA origami. Nyt software-værktøj til enkeltmolekyle-billeddannelse En af de centrale teknikker til karakterisering af dynamiske processer på nanoskalaen er Förster Resonance Energy Transfer (FRET) og Victoria Birkedal og hendes gruppe ved CDNA er eksperter i denne metode. I 2015 offentliggjorde de en artikel i Nature Methods om udviklingen af et nyt software-værktøj til enkelt-molekyle-FRET-studier.2 Den såkaldte iSMS software er et interaktiv værktøj til analyse af smFRET Total Internal Reflection Fluorescence(TIRF)-mikroskopi data. Softwaren behandler billeddata næsten 20 gange hurtigere

end de nuværende software-standarder og anvendes både parallelt med og efter dataopsamling En elektrokemisk kontrolleret DNA-struktur I samarbejde mellem Thom LaBean og to af CDNA-forskergrupperne i Aarhus er der udviklet en dynamisk DNA-origamistruktur som kan skiftes mellem to positioner under kontrol af pH-værdien.3 Konformationsændringen kunne også kontrolleres og aflæses elektronisk,og viser for første gang elektrokemisk aflæsning af DNA-origami-nanomekanik. Denne undersøgelse baner vejen for udviklingen af bioelektroniske nanoenheder, der udnytter DNA-origamimønstre på et ledende underlag.

Figur 2 Skematisk afbildning af (A) elektrokemisk opstilling til AFM og elektrokemisk karakterisering af DNA-origami på HOPG; (B) origamistruktur, der indeholder et pH-følsomt i-motiv i dens centrum; (C) en typisk i-motiv quadruplex struktur dannet i sure opløsninger; og (D) mulige konformationelle tilstande af origamistrukturen ved (a) pH 8 og (b og c) under pH 5. En DNA-baseret lommeregner I dette studie anvendes DNA til at udføre simple regnestykker. Resultatet fremkommer ikke ved en algoritme, men derimod ved en selektion af det rette resultat efter input af to DNA strenge der repræsenterer tal. Systemet returnerer resultatet som et tal i et display. Dette arbejde blev udført i et samarbejde mellem forskere ved Shanghai Institute of Applied Physics og CDNA og det blev offentliggjort i Nature Communications ved udgangen af 2015,4 Med yderligere udvikling, kan det potentielt set anvendes indenfor diagnostik, til at kombinere svar fra flere input.

Figure 3. Illustration af trinnene involveret i en multiplikation, hvor de to input DNA-strenge X og Y (F.eks. værdierne 1 og 2) bliver omdannet ved til en digital præsentation af resultatet. Referencer [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.