Integration of Switchable DNA-Based Hydrogels with Surfaces by the

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Integration of Switchable DNA-Based Hydrogels with Surfaces by the Hybridization Chain Reaction Jason S. Kahn, Alexander Trifonov, Alessandro Cecconello, Weiwei Guo, Chunhai Fan, and Itamar Willner Nano Lett., Just Accepted Manuscript • DOI: 10.1021/acs.nanolett.5b04101 • Publication Date (Web): 21 Oct 2015 Downloaded from http://pubs.acs.org on October 25, 2015

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Integration of Switchable DNA-Based Hydrogels with Surfaces by the Hybridization Chain Reaction

Jason S. Kahn, Alexander Trifonov, Alessandro Cecconello, Weiwei Guo, Chunhai Fan, and Itamar Willner*

Dr. J. Kahn, A. Trifonov, A. Cecconello, Dr. W. Guo, Prof. I. Willner Institute of Chemistry The Minerva Center for Complex Biohybrid Systems The Hebrew University of Jerusalem Jerusalem, 91904 (Israel) * To whom all correspondence should be addressed (e-mail: [email protected])

Prof. C. Fan Laboratory of Physical Biology Shanghai Institute of Applied Physics Chinese Academy of Sciences Shanghai 201800, China

ACS Paragon Plus Environment

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ABSTRACT: A novel method to assemble acrylamide/acrydite DNA copolymer hydrogels on surfaces, specifically gold-coated surfaces, is introduced. The method involves the synthesis of two different copolymer chains consisting of hairpin A, HA, modified acrylamide copolymer and hairpin B, HB, acrylamide copolymer. In the presence of a nucleic acid promoter monolayer associated with the surface, the hybridization chain reaction between the two hairpin-modified polymer chains is initiated, giving rise to the cross-opening of hairpins HA and HB and the formation of a crosslinked hydrogel on the surface. The co-functionalization of the HA- and HBmodified polymer chains with G-rich DNA tethers, that include the G-quadruplex subunits, hydrogels of switchable stiffness are generated. In the presence of K+ -ions, the hydrogel associated with the surface is cooperatively crosslinked by duplex units of HA and HB, and K+ion-stabilized G-quadruplex units, giving rise to a stiff hydrogel. The 18-crown-ether-stimulated elimination of the K+-ions dissociates the bridging G-quadruplex units, resulting in a hydrogel of reduced stiffness. The duplex/G-quadruplex cooperatively-stabilized hydrogel associated with the surface reveals switchable electrocatalytic properties. The incorporation of hemin into the Gquadruplex units of the duplex/G-quadruplex cooperatively electrocatalyzes the reduction of H2O2. The 18-crown-6-ether stimulated dissociation of the hemin/G-quadruplex bridging units leads to a catalytically-inactive hydrogel.

KEYWORDS: impedance spectroscopy; G-quadruplexes; stimuli-responsive; electrocatalysis; Young’s Modulus; acrylamide


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DNA-based hydrogels have attracted recent research interest as functional matrices for sensing and medical applications.1–7 Specifically, stimuli-responsive DNA-based hydrogels undergoing cyclic, and reversible, hydrogel/solution transitions were reported in the past few years. Different stimuli were applied as switches for the hydrogel-to-solution transitions, including pH,8–15 aptamer-ligand complexes,16,17 light,18–24 enzyme/DNAzymes,25 duplex/strand displacement,26 metal ion/ligands,27–31 and the formation/dissociation of G-quadruplexes in the presence of K+ ions/crown ether ligands.32 Applications of stimuli-responsive hydrogels span a wide range, including the controlled release of drugs,33 the use of hydrogels as sensors and actuators,34 the development of switchable catalytic materials,32 the development of shapememory hydrogels as inscription matrices,35,36 the controlled release of enzymes,37–39 and the activation of biocatalytic cascades.40 Two general strategies are involved in the preparation of DNA-based hydrogels. One approach involves the use of polydentate nucleic acid nanostructures, e.g., an X or Y-shaped DNA, that hybridize with themselves or duplex DNA units to form a tri-dimensional network of DNA subunits.41–43 A second approach involves the implementation of copolymer chains, e.g. copolymers composed of acrylamide/nucleic acid-functionalized acrylamide monomers, as polymer building blocks of the hydrogels.7,17,44 In these systems, the nucleic acid tethers associated with the copolymer chains carry the instructive information to crosslink the polymer chains and to form a three-dimensional hydrogel network. These crosslinking nucleic acid units can additionally be designed to include the instructive stimuli-responsive features that allow the formation and the separation of the hydrogels. Indeed, different stimuli such as K+ ion/crown ethers,32 pH,8–10 or metal ion (e.g., Ag+)/ligand (cysteamine)45 were applied to induce the formation and dissociation of acrylamide-DNA hydrogels through the crosslinking of the


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polymer chains. Gel formation and dissociation in these systems is controlled by K+-stabilized G-quadruplex formation and separation by the crown ether, the crosslinking of the chains by imotif bridges at acidic pH and separation at neutral pH or the pH-stimulated formation and dissociation of ‘hydrogels’ by triplex DNA bridges, and crosslinking by cooperative metal ionstabilized duplex (e.g., C-Ag+-C) and their separation by the ligand-assisted separation of the bridging complex. Stimuli-responsive, switchable DNA hydrogels were previously prepared and characterized as bulk matrices that were formed in solution. The generation of switchable DNA hydrogel films on surfaces could be a rational path to control interfacial properties and functions by means of a hydrogel. While physical adhesion of hydrogels on surfaces is feasible (e.g. spin-coating),46,47 the separation of the matrices from the surface upon switchable hydrogel/solution transitions remains a limitation, and thus the assembly of surface-integrated switchable polymer assemblies undergoing hydrogel/solution transitions is a challenging goal. Here we wish to report on the application of the hybridization chain reaction (HCR)48,49 as a route to assemble surfaceintegrated acrylamide/DNA hydrogels. Through the appropriate design, the DNA-modified hydrogels are assembled as surface-integrated hydrogels with switchable functionalities. Specifically, we demonstrate the integration of K+ ion/crown ether switchable hydrogels on electrode surfaces and switchable electrocatalytic properties through the formation of a hemin/Gquadruplex-modified electrocatalytic hydrogel. The method to assemble the hydrogel on an electrode surface is depicted in Figure 1(A) and is based on the hybridization chain reaction (HCR). The hybridization chain reaction,48,49 developed by Pierce, involves the probe-initiated cross-opening of two hairpin structures to yield polymer nucleic acid wires. That is, the two hairpins, HA and HB, are programmed to include caged sequences that can cross-interact with


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each other to yield the polymer wire. A nucleic acid initiator triggers the opening of HA, and consequently the uncaging of the sequence that opens HB. The uncaged HB includes the sequence for the opening of HA, thus initiating the sequential cross-opening of the hairpins and the assembly of the wires. This process was applied to develop amplified DNA sensing platforms,50,51 to assemble DNA nanostructures,52–54 and to operate logic gates.55,56 Accordingly, acrylamide monomer units were copolymerized with acrydite-modified DNA monomers to form polymers P1 and P2. P1 incorporates (1), where (1) exists as hairpin DNA structure HA, and P2 incorporates (3), a short tether that hybridizes to (2), which exists as HB. The tethered P2 system is necessary due to the capability to only add the acrydite functional group to the 5’-end of the DNA; in order to maintain the direction of the HCR off of the surface, (2) was not directly polymerized into the acrylamide-DNA copolymer as is (1), but hybridized after polymerization to (3) to form the final hairpin unit (2)/(3). The copolymerization reactions were performed at a ratio of 2% acrylamide:0.5 mM acrydite nucleic acid. The molecular weights of the resulting (1)acrylamide and (3)-acrylamide copolymers corresponded to ca. 370 kDa and 85 kDa, respectively, and the DNA loading was evaluated to be 450:1 acrylamide:(1) and 425:1 acrylamide:(2)/(3), respectively (for the determination of the molecular weights and the loading ratio of the respective nucleic acids see Experimental Section and Figures S1-S3). The Au-coated electrode surfaces were modified with the nucleic acid initiator (4), which is complementary to the toehold region of hairpin HA. Surface coverage of (4) was measured to be ca. 25 pmoles!cm-2, as determined using quartz crystal monitor (QCM) analysis and calculated with the Sauerbrey equation.57 Hybridization of (4) with HA uncages the domain complementary to the toehold region of HB. The hybridization with HB uncages the domain of HB that is complementary to the toehold of HA. As a result, the initiator-stimulated opening of HA triggers


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the cross-opening between HA and HB, leading to crosslinked polymer hydrogel films attached to the surface through the two chains. The formation of the hydrogel was followed by Faradaic impedance spectroscopy,58,59 Figure 1(B), and by SEM imaging, Figure 1(C). Figure 1(B) depicts the time-dependent Faradaic impedance spectra of the modified electrode (in the form of Nyquist plots) upon the build-up of the hydrogel film, where Fe(CN)63-/4- is used as a redox-label. The (4)-monolayer modified electrode shows a small interfacial electron transfer resistance, and as the build-up of the hydrogel film proceeds, the interfacial electron transfer resistance increases, consistent with the formation of an insulating polymer film that includes nucleic acid units that repel the redox label. This build-up of the hydrogel was also tracked using QCM measurements, where a mass change of 6.30 micrograms was measured after 1 hour of gelation. Rheometry characterization of the film indicates a Young’s Modulus of 317 ± 14 Pa for the film. The SEM image of the freeze-dried, metal-coated hydrogel film is shown in Figure 1(C), Panel I. A porous structure of the hydrogel film is observed. The cross section analysis of the resulting film, Panel II, indicates a film thickness up to 100 microns. Further support that the hydrogel film is indeed generated by the cross-opening HCR process of the two polymer chains, carrying hairpins HA and HB, is obtained by staining the reaction products with a DNA specific fluorescent dye, Figure S4. The treatment of the (4)-modified surface with only P1 yields low fluorescence consistent with monolayer coverage of duplex units between (4) and opened HA. Treatment of the (4)-functionalized surface with only P2 did not yield fluorescence, consistent with the lack of interactions between (4) and HB. The staining of the (4)-modified surface subjected to the two chains P1 and P2 yields an intense fluorescence signal, consistent with the formation of a duplex-bridged network generated by the HCR process. Further support of these results is shown in Figure S5, showing the greatest increase in Faradeic impedance over time in


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the system containing both P1 and P2 and a smaller increase during only P1 incubation. The specificity system of the system is also shown, as incubation of an unmodified gold surface with both P1 and P2 reveals a negligible change in impedance. The successful deposition of the acrylamide/acrydite nucleic acid hydrogel films on Au surfaces, using the HCR process, was then implemented to generate stimuli-responsive hydrogel films on surfaces, exhibiting switchable interfacial electron transfer properties and switchable electrocatalytic properties, Figure 2. Two copolymer acrylamide chains, P1G and P2G, were prepared. Polymer chain P1G is composed of acrylamide monomer units, monomer units composed of hairpin HA (1), and (5), an acrydite-G-rich-nucleic acid monomer (where (5) consists of a subunit of the G-quadruplex). The copolymer chain P2G is composed of the acrylamide monomer, the (2)/(3) monomer presenting hairpin HB, and (5). Both P1G and P2G polymers were prepared using the same formulation as previously discussed with the addition of 1 mM (5) (giving a 2:1 G-quadruplex subunit:hairpin ratio), and possessed molecular weights of 515 kDa and 70 kDa, respectively. The (4)-modified Au surface triggers the HCR process in the presence of the chains P1G and P2G. Figure 2(B) depicts the time-dependent Faradaic impedance spectra upon the (4)-triggered, HCR-induced formation of the polymer film in the presence of the polymer chains P1G and P2G, in the absence of K+ ions. As the time-interval of the HCR process is prolonged, the interfacial electron transfer resistances increase, consistent with the build-up of the nucleic acid crosslinked acrylamide film and the increase in the negative charge associated with the nucleic acids being integrated as a part of the film. After gel formation, addition of K+ ions leads to the formation of K+-stabilized G-quadruplex, yielding a rigidified hydrogel stabilized by cooperative bridging units consisting of the duplex nucleic acids formed by the HCR process, (1)/(2), and the K+-stabilized G-quadruplex, (5)/(5), Figure 2(A). Further


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addition to the resulting hydrogel-film-modified surface of 18-crown-6-ether eliminates the K+ from the G-quadruplex units, leading to a less rigid polymer film. By the cyclic addition of K+ and 18-crown-6-ether to the system, the film is switched between hydrogel states of high and low stiffness, respectively. The change in stiffness can be seen in the switchable Young’s modulus of the films, whereby before K+ addition, the (1)/(2) crosslinked gel possesses a Young’s modulus of 461 ± 134 Pa, and after K+ addition, the Young’s modulus of the (1)/(2) and (5)/(5)-K+stabilized G-quadruplex film is 1.77 kPa ± 174 Pa, as shown in Figure 2(C). Further addition of the respective components demonstrates the cyclic switching of the hydrogel. The kinetics of the switching process after addition of crown ether is demonstrated in Figure S6, and clearly shows the reduction of the Young’s modulus over time. The SEM images of the switchable hydrogel states are depicted in Figure 2(D). The K+-stabilized gel maintains a high density pore network under the conditions required for SEM imaging, notably freeze drying, and thus while the hydrogel coating reveals a network before addition of K+, Figure 2(D)-Panel I, the increase in gel strength after K+ ion incubation can be seen in Panel II by the higher density, small porous network. Such support for gel strength and pore size comparison was found in previous work regarding shape memory hydrogels.36 The successful deposition of the hairpin stabilized hydrogel, cooperatively crosslinked with G-quadruplex bridges and possessing the capability to switch between higher and lower stiffness states, was further applied to develop a switchable electrocatalytic film. Previous studies have demonstrated that the association of hemin with G-quadruplexes yields an electrocatalyst for the reduction of H2O2 to water.60 This process was implemented to develop amplified electrochemical sensing platforms for DNA60 or aptamer-ligand complexes,60 as well as for the probing of the dynamic mechanical transitions of a DNA “walker” on electrode surfaces.61


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Accordingly, the switchable K+-stabilized G-quadruplex crosslinked hydrogel was implemented to develop an electrocatalytic switchable film, Figure 3(A). The association of hemin to the K+stabilized G-quadruplex yields the electrocatalytic film that stimulates the electrocatalyzed reduction of H2O2 to water. Treatment of the hydrogel film with 18-crown-6-ether removes the K+ ions from the quadruplex structure, resulting in the separation of the hemin/G-quadruplex electrocatalyst and the generation of the catalytically inactive state. Figure 3(B), Curve (I), shows the cyclic voltammogram of the prepared (1)/(2) and (5)/(5) crosslinked film in the presence of added hemin and H2O2. No electrocatalytic current is observed, consistent with the formation of a gel state that is not crosslinked by the hemin/G-quadruplex. Addition of K+ ions and hemin to the system, in the presence of H2O2, results in the more rigid gel state with cooperative crosslinking and produces the cyclic voltammogram shown in Figure 3(B), Curve (II). Further addition of 18-crown-6-ether to the system removes the K+ ions from the electrocatalytic gel, dissociating the G-quadruplex and leading to the less rigid gel state lacking electrocatalytic activities, Figure 3(B), Curve (III). By the cyclic treatment of the nucleic acidfunctionalized electrode with K+ ions and 18-crown-6-ether, the film is switched between electrocatalytically-active, “ON”, and inactive, “OFF”, states, as shown by the impedance switching in Figure 3(C). To conclude, the present study has introduced a novel method to prepare surface-confined hydrogel films by employing the hybridization chain reaction using copolymers of acrylamide and acrydite nucleic acids. By the synthesis of hydrogel films that are cooperatively stabilized by duplex and G-quadruplex bridges, the switchable transition of the film between rigid (in the presence of K+ ions) and less rigid (in the presence of 18-crown-6-ether) states has been demonstrated. The switchable transitions of the surface-associated films were found to control


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the interfacial electron transfer properties and the electrocatalytic functions of the hydrogelmodified electrodes.

ASSOCIATED CONTENT Supporting Information. The following files are available free of charge. Materials and Methods (PDF)

AUTHOR INFORMATION Corresponding Author *E-mail: [email protected]. Tel: 972-2-6585272. Fax: 972- 2-6527715. Author Contributions The manuscript was written through contributions of all authors. All authors have given approval to the final version of the manuscript. Notes The authors declare no competing financial interest.

ACKNOWLEDGMENT This research is supported by the EU FET Open MICREAGENT Project. J.S.K. acknowledges the Lady Davis Postdoctoral Fellowship, The Hebrew University of Jerusalem.


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REFERENCES (1)

Liu, J. Oligonucleotide-Functionalized Hydrogels as Stimuli Responsive Materials and Biosensors. Soft Matter 2011, 7, 6757–6767.

(2)

Roh, Y. H.; Ruiz, R. C. H.; Peng, S.; Lee, J. B.; Luo, D. Engineering DNA-Based Functional Materials. Chem. Soc. Rev. 2011, 40, 5730–5744.

(3)

Okay, O. DNA Hydrogels: New Functional Soft Materials. J. Polym. Sci. Part B: Polym. Phys. 2011, 49, 551–556.

(4)

Lin, D. C.; Yurke, B.; Langrana, N. A. Mechanical Properties of a Reversible, DNACrosslinked Polyacrylamide Hydrogel. J. Biomech. Eng. 2004, 126, 104–110.

(5)

Tang, H.; Duan, X.; Feng, X.; Liu, L.; Wang, S.; Li, Y.; Zhu, D. Fluorescent DNAPoly(phenylenevinylene) Hybrid Hydrogels for Monitoring Drug Release. Chem. Commun. 2009, 641–643.

(6)

Murakami, Y.; Maeda, M. DNA-Responsive Hydrogels That Can Shrink or Swell. Biomacromolecules 2005, 6, 2927–2929.

(7)

Wei, B.; Cheng, I.; Luo, K. Q.; Mi, Y. Capture and Release of Protein by a Reversible DNA-Induced Sol–Gel Transition System. Angew. Chem. Int. Ed. 2008, 47, 331–333.

(8)

Cheng, E.; Xing, Y.; Chen, P.; Yang, Y.; Sun, Y.; Zhou, D.; Xu, L.; Fan, Q.; Liu, D. A pH-Triggered, Fast-Responding DNA Hydrogel. Angew. Chem. Int. Ed. 2009, 48, 7660– 7663.

(9)

Ren, J.; Hu, Y.; Lu, C.-H.; Guo, W.; Aleman-Garcia, M. A.; Ricci, F.; Willner, I. pHResponsive and Switchable Triplex-Based DNA Hydrogels. Chem. Sci. 2015, 6, 4190– 4195.

(10)

Guo, W.; Lu, C.-H.; Qi, X.-J.; Orbach, R.; Fadeev, M.; Yang, H.-H.; Willner, I. Switchable Bifunctional Stimuli-Triggered Poly-N-Isopropylacrylamide/DNA Hydrogels. Angew. Chem. Int. Ed. 2014, 53, 10134–10138.

(11)

Liu, D.; Balasubramanian, S. A Proton-Fuelled DNA Nanomachine. Angew. Chem. Int. Ed. 2003, 42, 5734–5736.

(12)

Sharma, J.; Chhabra, R.; Yan, H.; Liu, Y. pH-Driven Conformational Switch of “I-Motif” DNA for the Reversible Assembly of Gold Nanoparticles. Chem. Commun. 2007, 477– 479.

(13)

Wang, W.; Yang, Y.; Cheng, E.; Zhao, M.; Meng, H.; Liu, D.; Zhou, D. A pH-Driven, Reconfigurable DNA Nanotriangle. Chem. Commun. 2009, 824–826.


11

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1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 12 of 20

(14)

Wang, C.; Huang, Z.; Lin, Y.; Ren, J.; Qu, X. Artificial DNA Nano-Spring Powered by Protons. Adv. Mater. 2010, 22, 2792–2798.

(15)

Shimron, S.; Magen, N.; Elbaz, J.; Willner, I. pH-Programmable DNAzyme Nanostructures. Chem. Commun. 2011, 47, 8787–8789.

(16)

Yang, H.; Liu, H.; Kang, H.; Tan, W. Engineering Target-Responsive Hydrogels Based on Aptamer−Target Interactions. J. Am. Chem. Soc. 2008, 130, 6320–6321.

(17)

Zhu, Z.; Wu, C.; Liu, H.; Zou, Y.; Zhang, X.; Kang, H.; Yang, C. J.; Tan, W. An Aptamer Cross-Linked Hydrogel as a Colorimetric Platform for Visual Detection. Angew. Chem. Int. Ed. 2010, 49, 1052–1056.

(18)

Liu, Y.; Sen, D. A Contact Photo-Cross-Linking Investigation of the Active Site of the 817 Deoxyribozyme. J. Mol. Biol. 2008, 381, 845–859.

(19)

Liang, X.; Nishioka, H.; Takenaka, N.; Asanuma, H. A DNA Nanomachine Powered by Light Irradiation. ChemBioChem 2008, 9, 702–705.

(20)

Kang, H.; Liu, H.; Phillips, J. A.; Cao, Z.; Kim, Y.; Chen, Y.; Yang, Z.; Li, J.; Tan, W. Single-DNA Molecule Nanomotor Regulated by Photons. Nano Lett. 2009, 9, 2690–2696.

(21)

Han, D.; Huang, J.; Zhu, Z.; Yuan, Q.; You, M.; Chen, Y.; Tan, W. Molecular Engineering of Photoresponsive Three-Dimensional DNA Nanostructures. Chem. Commun. 2011, 47, 4670–4672.

(22)

Yang, Y.; Endo, M.; Hidaka, K.; Sugiyama, H. Photo-Controllable DNA Origami Nanostructures Assembling into Predesigned Multiorientational Patterns. J. Am. Chem. Soc. 2012, 134, 20645–20653.

(23)

You, M.; Huang, F.; Chen, Z.; Wang, R.-W.; Tan, W. Building a Nanostructure with Reversible Motions Using Photonic Energy. ACS Nano 2012, 6, 7935–7941.

(24)

Zou, Y.; Chen, J.; Zhu, Z.; Lu, L.; Huang, Y.; Song, Y.; Zhang, H.; Kang, H.; Yang, C. J. Single-Molecule Photon-Fueled DNA Nanoscissors for DNA Cleavage Based on the Regulation of Substrate Binding Affinity by Azobenzene. Chem. Commun. 2013, 49, 8716–8718.

(25)

Lin, H.; Zou, Y.; Huang, Y.; Chen, J.; Zhang, W. Y.; Zhuang, Z.; Jenkins, G.; Yang, C. J. DNAzyme Crosslinked Hydrogel: A New Platform for Visual Detection of Metal Ions. Chem. Commun. 2011, 47, 9312–9314.

(26)

Liedl, T.; Dietz, H.; Yurke, B.; Simmel, F. Controlled Trapping and Release of Quantum Dots in a DNA-Switchable Hydrogel. Small 2007, 3, 1688–1693.


12

Page 13 of 20

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

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(27)

Monchaud, D.; Yang, P.; Lacroix, L.; Teulade-Fichou, M.-P.; Mergny, J.-L. A MetalMediated Conformational Switch Controls G-Quadruplex Binding Affinity. Angew. Chem. Int. Ed. 2008, 47, 4858–4861.

(28)

Ono, A.; Cao, S.; Togashi, H.; Tashiro, M.; Fujimoto, T.; Machinami, T.; Oda, S.; Miyake, Y.; Okamoto, I.; Tanaka, Y. Specific Interactions between Silver(i) Ions and Cytosine-Cytosine Pairs in DNA Duplexes. Chem. Commun. 2008, 4825–4827.

(29)

Han, D.; Kim, Y.-R.; Oh, J.-W.; Kim, T. H.; Mahajan, R. K.; Kim, J. S.; Kim, H. A Regenerative Electrochemical Sensor Based on Oligonucleotide for the Selective Determination of Mercury(ii). Analyst 2009, 134, 1857–1862.

(30)

Li, T.; Shi, L.; Wang, E.; Dong, S. Silver-Ion-Mediated DNAzyme Switch for the Ultrasensitive and Selective Colorimetric Detection of Aqueous Ag+ and Cysteine. Chem. Eur. J. 2009, 15, 3347–3350.

(31)

Shimron, S.; Elbaz, J.; Henning, A.; Willner, I. Ion-Induced DNAzyme Switches. Chem. Commun. 2010, 46, 3250–3252.

(32)

Lu, C.-H.; Qi, X.-J.; Orbach, R.; Yang, H.-H.; Mironi-Harpaz, I.; Seliktar, D.; Willner, I. Switchable Catalytic Acrylamide Hydrogels Cross-Linked by Hemin/G-Quadruplexes. Nano Lett. 2013, 13, 1298–1302.

(33)

Soontornworajit, B.; Zhou, J.; Zhang, Z.; Wang, Y. Aptamer-Functionalized In Situ Injectable Hydrogel for Controlled Protein Release. Biomacromolecules 2010, 11, 2724– 2730.

(34)

Joseph, K. A.; Dave, N.; Liu, J. Electrostatically Directed Visual Fluorescence Response of DNA-Functionalized Monolithic Hydrogels for Highly Sensitive Hg2+ Detection. ACS Appl. Mater. Interfaces 2011, 3, 733–739.

(35)

Lee, J. B.; Peng, S.; Yang, D.; Roh, Y. H.; Funabashi, H.; Park, N.; Rice, E. J.; Chen, L.; Long, R.; Wu, M.; et al. A Mechanical Metamaterial Made from a DNA Hydrogel. Nat. Nanotech 2012, 7, 816–820.

(36)

Guo, W.; Lu, C.-H.; Orbach, R.; Wang, F.; Qi, X.-J.; Cecconello, A.; Seliktar, D.; Willner, I. pH-Stimulated DNA Hydrogels Exhibiting Shape-Memory Properties. Adv. Mater. 2015, 27, 73–78.

(37)

Kopeček, J.; Yang, J. Smart Self-Assembled Hybrid Hydrogel Biomaterials. Angew. Chem. Int. Ed. 2012, 51, 7396–7417.

(38)

Lee, K. Y.; Mooney, D. J. Hydrogels for Tissue Engineering. Chem. Rev. 2001, 101, 1869–1880.


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Page 14 of 20

(39)

Peppas, N. A.; Hilt, J. Z.; Khademhosseini, A.; Langer, R. Hydrogels in Biology and Medicine: From Molecular Principles to Bionanotechnology. Adv. Mater. 2006, 18, 1345– 1360.

(40)

Lilienthal, S.; Shpilt, Z.; Wang, F.; Orbach, R.; Willner, I. Programmed DNAzymeTriggered Dissolution of DNA-Based Hydrogels: Means for Controlled Release of Biocatalysts and for the Activation of Enzyme Cascades. ACS Appl. Mater. Interfaces 2015, 7, 8923–8931.

(41)

Um, S. H.; Lee, J. B.; Park, N.; Kwon, S. Y.; Umbach, C. C.; Luo, D. Enzyme-Catalysed Assembly of DNA Hydrogel. Nat. Mater. 2006, 5, 797–801.

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Park, N.; Kahn, J. S.; Rice, E. J.; Hartman, M. R.; Funabashi, H.; Xu, J.; Um, S. H.; Luo, D. High-Yield Cell-Free Protein Production from P-Gel. Nat. Protoc. 2009, 4, 1759–1770.

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Xing, Y.; Cheng, E.; Yang, Y.; Chen, P.; Zhang, T.; Sun, Y.; Yang, Z.; Liu, D. SelfAssembled DNA Hydrogels with Designable Thermal and Enzymatic Responsiveness. Adv. Mater. 2011, 23, 1117–1121.

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Yan, L.; Zhu, Z.; Zou, Y.; Huang, Y.; Liu, D.; Jia, S.; Xu, D.; Wu, M.; Zhou, Y.; Zhou, S.; et al. Target-Responsive “Sweet” Hydrogel with Glucometer Readout for Portable and Quantitative Detection of Non-Glucose Targets. J. Am. Chem. Soc. 2013, 135, 3748–3751.

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Guo, W.; Qi, X.-J.; Orbach, R.; Lu, C.-H.; Freage, L.; Mironi-Harpaz, I.; Seliktar, D.; Yang, H.-H.; Willner, I. Reversible Ag+-Crosslinked DNA Hydrogels. Chem. Commun. 2014, 50, 4065–4068.

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Tokarev, I.; Minko, S. Stimuli-Responsive Hydrogel Thin Films. Soft Matter 2009, 5, 511–524.

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White, E. M.; Yatvin, J.; Grubbs, J. B.; Bilbrey, J. A.; Locklin, J. Advances in Smart Materials: Stimuli-Responsive Hydrogel Thin Films. J. Polym. Sci. Part B: Polym. Phys. 2013, 51, 1084–1099.

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Dirks, R. M.; Pierce, N. A. Triggered Amplification by Hybridization Chain Reaction. Proc. Nat. Acad. Sci., U.S.A. 2004, 101 , 15275–15278.

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Wang, F.; Lu, C.-H.; Willner, I. From Cascaded Catalytic Nucleic Acids to Enzyme–DNA Nanostructures: Controlling Reactivity, Sensing, Logic Operations, and Assembly of Complex Structures. Chem. Rev. 2014, 114, 2881–2941.

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Shimron, S.; Wang, F.; Orbach, R.; Willner, I. Amplified Detection of DNA through the Enzyme-Free Autonomous Assembly of Hemin/G-Quadruplex DNAzyme Nanowires. Anal. Chem. 2012, 84, 1042–1048.


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Wang, F.; Elbaz, J.; Orbach, R.; Magen, N.; Willner, I. Amplified Analysis of DNA by the Autonomous Assembly of Polymers Consisting of DNAzyme Wires. J. Am. Chem. Soc. 2011, 133, 17149–17151.

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Venkataraman, S.; Dirks, R. M.; Rothemund, P. W. K.; Winfree, E.; Pierce, N. A. An Autonomous Polymerization Motor Powered by DNA Hybridization. Nat. Nanotech 2007, 2, 490–494.

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Yin, P.; Choi, H. M. T.; Calvert, C. R.; Pierce, N. A. Programming Biomolecular SelfAssembly Pathways. Nature 2008, 451, 318–322.

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Yurke, B.; Turberfield, A. J.; Mills, A. P.; Simmel, F. C.; Neumann, J. L. A DNA-Fuelled Molecular Machine Made of DNA. Nature 2000, 406, 605–608.

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Qian, L.; Winfree, E. Scaling Up Digital Circuit Computation with DNA Strand Displacement Cascades. Science 2011, 332 , 1196–1201.

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Orbach, R.; Wang, F.; Lioubashevski, O.; Levine, R. D.; Remacle, F.; Willner, I. A FullAdder Based on Reconfigurable DNA-Hairpin Inputs and DNAzyme Computing Modules. Chem. Sci. 2014, 5, 3381–3387.

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Alfonta, L.; Willner, I.; Throckmorton, D. J.; Singh, A. K. Electrochemical and Quartz Crystal Microbalance Detection of the Cholera Toxin Employing Horseradish Peroxidase And GM1-Functionalized Liposomes. Anal. Chem. 2001, 73, 5287–5295.

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K’Owino, I. O.; Sadik, O. A. Impedance Spectroscopy: A Powerful Tool for Rapid Biomolecular Screening and Cell Culture Monitoring. Electroanalysis 2005, 17, 2101– 2113.

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Katz, E.; Willner, I. Probing Biomolecular Interactions at Conductive and Semiconductive Surfaces by Impedance Spectroscopy: Routes to Impedimetric Immunosensors, DNASensors, and Enzyme Biosensors. Electroanalysis 2003, 15, 913–947.

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Pelossof, G.; Tel-Vered, R.; Elbaz, J.; Willner, I. Amplified Biosensing Using the Horseradish Peroxidase-Mimicking DNAzyme as an Electrocatalyst. Anal. Chem. 2010, 82, 4396–4402.

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Liu, X.; Niazov-Elkan, A.; Wang, F.; Willner, I. Switching Photonic and Electrochemical Functions of a DNAzyme by DNA Machines. Nano Lett. 2013, 13, 219–225.


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Figure 1: (A) Scheme for the deposition of the acrylamide-acrydite nucleic acid hybrid hydrogel on a Au-coated glass surface using the hybridization chain reaction (HCR). (B) Time-dependent Faradaic impedance spectra, in the form of Nyquist plots, recorded upon the deposition of the acrylamide-acrydite nucleic acid hydrogel on the Au surface at different time-intervals of the HCR process: (a) 0 minutes (b) 15 minutes (c) 45 minutes (d) 75 minutes. Spectra recorded in the presence of 25 mM HEPES, pH 7.2, 25 mM MgCl2 using a 2 mM Fe(CN)63-/4- (1:1)-mixture under a bias potential of 0.175 V and perturbation potential of 10 mV. (C) SEM images corresponding to: (I) The acrylamide-acrydite nucleic acid hydrogel film. (II) Cross sectional


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analysis of the resulting hydrogel film. Samples prepared by freeze-drying in liquid nitrogen followed by Au/Pd sputter coating with a time interval of 20 seconds.

Figure 2: (A) Scheme for the deposition of a G-quadruplex switchable hydrogel on a Au-coated glass surface exhibiting controlled stiffness properties. (B) Time-dependent Faradaic impedance spectra, in the form of Nyquist plots, corresponding to the build-up of the (1)/(2)-crosslinked hydrogel containing (5) at different time-intervals of the HCR process: (a) 0 minutes (b) 15 minutes (c) 45 minutes (d) 75 minutes. Spectra recorded in the presence of 25 mM HEPES, pH


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7.2, 25 mM MgCl2 using a 2 mM Fe(CN)63-/4- (1:1)-mixture under a bias potential of 0.175 V and perturbation potential of 10 mV. (C) The switching of Young’s modulus corresponding to the (I) (1)/(2) crosslinked-acrydite nucleic acid hydrogel and to the (II) K+-cooperatively crosslinked (1)/(2) and (5)/(5) G-quadruplex hydrogel. (D) SEM images corresponding to: (I) The Gquadruplex switchable hydrogel film before K+ incubation. (II) The G-quadruplex switchable hydrogel film after K+ incubation. Samples prepared by freeze-drying in liquid nitrogen followed by Au/Pd sputter coating with a time interval of 20 seconds.

Figure 3: (A) Switchable electrocatalytic function of the (1)/(2) and (5)/(5) cooperatively stabilized hemin/G-Quadruplex acrylamide-acrydite nucleic acid hydrogel. In the presence of K+ ions, the (1)/(2) and (5)/(5)-hemin/G-quadruplex units crosslink the hydrogel structure, leading


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to the electrocatalytic reduction of H2O2 by the hemin/G-quadruplex. Addition of 18-crown-6ether to the system results in the dissociation of the hemin/G-quadruplex and to the switching of the electrocatalytic functions of the hydrogel. (B) Cyclic voltammograms corresponding to: (I) The electrocatalytic inactive configuration of the (1)/(2) and (5)/(5) crosslinked hydrogel in the presence of 20 mM K+, but in the absence of hemin. (II) After the addition of hemin, 1 mM, to the system. (III) After addition of 18-crown-6-ether, 22 mM, resulting in the dissociation of the hemin/G-quadruplex units. (IV) After re-addition of K+ ions, 24 mM, resulting in the regeneration of the hemin/G-quadruplex units. Experiment was performed in 1 mM H2O2 in a buffered solution of 25 mM HEPES, pH 7.2, 25 mM MgCl2, kept under nitrogen bubbling. (C) Cyclic switchable ‘ON’/‘OFF’ activation of the electrocatalytic functions of the acrylamide(1)/(2) and (5)/(5)-hemin/G-quadruplex cooperatively crosslinked hydrogel. Impedance measurements recorded in the presence of 25 mM HEPES, pH 7.2, 25 mM MgCl2 using a 2 mM Fe(CN)63-/4- (1:1)-mixture under a bias potential of 0.175 V and perturbation potential of 10 mV.


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ToC Entry:

Au surfaces modified with a nucleic acid initiator induce the hybridization chain reaction between two-hairpin-functionalized acrylamide polymer chains (P1 and P2), leading to the assembly of DNA-based hydrogels on the surface. Incorporation of G-rich tethers into hairpinfunctionalized polymers (P1G and P2G) forms hydrogels of switchable stiffness in the presence of K+/18-crown-6-ether, and further integration of hemin yields switchable electrocatalytic hydrogels.


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Integration of Switchable DNA-Based Hydrogels with Surfaces by the

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