Light-Driven DNA Nanomachine with a Photoresponsive Molecular Engine Yukiko Kamiya †,‡ and Hiroyuki Asanuma* ,† † Graduate School of Engineering, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8603 Japan ‡ Ecotopia Science Institute, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8603 Japan CONSPECTUS: DNA is regarded as an excellent nanoma- terial due to its supramolecular property of duplex formation through A-T and G-C complementary pairs. By simply designing sequences, we can create any desired 2D or 3D nanoarchitecture with DNA. Based on these nanoarchitectures, motional DNA-based nanomachines have also been developed. Most of the nanomachines require molecular fuels to drive them. Typically, a toehold exchange reaction is applied with a complementary DNA strand as a fuel. However, repetitive operation of the machines accumulates waste DNA duplexes in the solution that gradually deteriorate the motional efficiency. Hence, we are facing an “environmental problem” even in the nanoworld. One of the direct solutions to this problem is to use clean energy, such as light. Since light does not contaminate the reaction system, a DNA nanomachine run by a photon engine can overcome the drawback of waste that is a problem with molecular-fueled engines. There are several photoresponsive molecules that convert light energy to mechanical motion through the change of geometry of the molecules; these include spiropyran, diarylethene, stilbene, and azobenzene. Although each molecule has both advantages and drawbacks, azobenzene derivatives are widely used as “molecular photon engines”. In this Account, we review light-driven DNA nanomachines mainly focusing on the photoresponsive DNAs that we have developed for the past decade. The basis of our method is installation of an azobenzene into a DNA sequence through a D-threoninol scaffold. Reversible hybridization of the DNA duplex, triggered by trans-cis isomerization of azobenzene in the DNA sequences by irradiation with light, induces mechanical motion of the DNA nanomachine. Moreover we have successfully developed azobenzene derivatives that improve its photoisomerizaition properties. Use of these derivatives and techniques have allowed us to design various DNA machines that demonstrate sophisticated motion in response to lights of different wavelengths without a drop in photoregulatory efficiency. In this Account, we emphasize the advantages of our methods including (1) ease of preparation, (2) comprehensive sequence design of azobenzene-tethered DNA, (3) efficient photoisomerization, and (4) reversible photocontrol of hybridization by irradiation with appropriate wavelengths of light. We believe that photon-fueled DNA nanomachines driven by azobenzene- derivative molecular photon-fueled engines will be soon science rather than “science fiction”. ■ INTRODUCTION Beyond its biological importance, DNA is recognized as an exciting material in nanotechnology due to facile programm- ability. Various DNA nanoarchitectures have been designed by assembling DNA in combination with organic molecules to supply missing functions to DNA. 1-7 Among DNA-based nanoarchitectures, nanosized motional machines have been developed by using DNA as a scaffold for nanobodies such as tweezers, walkers, and gears. 8-15 Like machines in the macroscopic “meter-scale world”, nanomachines are also subject to the law of conservation of energy. One type of engine used to drive these DNA-based nanomachines is fueled by spontaneous hybridization of DNA with its complementary strand. Yurke et al. first demonstrated tweezer-like motion using an engine driven by reversible opening and closing of two handles (Figure 1). 9 The two handles close upon hybridization of two overhangs with the added DNA fuel F. Closed tweezers are reset to the initial open state by the toehold exchange with another DNA fuel F producing F/ F waste duplexes. Most nucleotide-based nanomachines are driven by the toehold exchange method. However, repetitive motions accumulate F/ F waste duplexes in the solution, which contaminates the microenvironment and retards driving efficiency. 9 Hence, the “nanoworld” faces environmental problems similar to those of the “meter world”. One of the solutions to environmental problems is use of clean energy sources that do not contaminate the nanoenvironment such as electricity, protons, or light. pH-driven nanomachines equipped with pH-sensitive DNA architectures such as i-motif minimize contamination. 15,16 Among the energy sources listed above, light is the most promising, because light does not contaminate the reaction system, and its use makes spatiotemporal control of bio- reactions possible. 17 In this Account, we first introduce several photochromic compounds with potential as photon engines and then focus on recent progress on the conversion of light energy into mechanical motion. Special Issue: Nucleic Acid Nanotechnology Received: December 21, 2013 Published: March 11, 2014 Article pubs.acs.org/accounts © 2014 American Chemical Society 1663 dx.doi.org/10.1021/ar400308f | Acc. Chem. Res. 2014, 47, 1663-1672