Microchemomechanical devices usingDNA hybridizationGuolong Zhua,1

, Mark Hannela, Ruojie Shab, Feng Zhoua, Matan Yah Ben Ziona

, Yin Zhanga, Kyle Bishopc,

David Griera, Nadrian Seemanb,1, and Paul Chaikina,1

aDepartment of Physics, New York University, New York, NY 10003; bDepartment of Chemistry, New York University, New York, NY 10003;and cDepartment of Chemical Engineering, Columbia University, New York, NY 10027

Edited by Oleg Gang, Columbia University, New York, NY, and accepted by Editorial Board Member Joanna Aizenberg April 15, 2021 (received for reviewNovember 18, 2020)

The programmability of DNA oligonucleotides has led to sophis-ticated DNA nanotechnology and considerable research on DNAnanomachines powered by DNA hybridization. Here, we investi-gate an extension of this technology to the micrometer-colloidalscale, in which observations and measurements can be made inreal time/space using optical microscopy and holographic opticaltweezers. We use semirigid DNA origami structures, hinges withmechanical advantage, self-assembled into a nine-hinge, accordion-like chemomechanical device, with one end anchored to a substrateand a colloidal bead attached to the other end. Pulling the beadconverts the mechanical energy into chemical energy stored byunzipping the DNA that bridges the hinge. Releasing the beadreturns this energy in rapid (>20 μm/s) motion of the bead. Force-extension curves yield energy storage/retrieval in these devices thatis very high. We also demonstrate remote activation and sensing—pulling the bead enables binding at a distant site. This work opensthe door to easily designed and constructed micromechanical de-vices that bridge the molecular and colloidal/cellular scales.

soft condensed matter | DNA nanotechnology | colloidal physics |microchemomechanical devices | self-assembly

Force, motion, and work are ubiquitously produced in livingorganisms by molecular motors fueled by ATP. Hydrolysis of

ATP at ∼20 kBT/molecule is consumed by motors with <50%efficiency generating forces of 2 to 8 pN (1); DNA hybridizationproduces forces of 8 to 20 pN and supplies energies of 2 to 5 kBTper nucleotide (nt) pair (2). The comparable numbers suggestthat DNA hybridization may prove a useful way to powermicrodevices or store energy microscopically, particularly sincethe fuel and mechanical device can be the same molecule. Pre-vious DNA devices (3–5) are important demonstrations typicallyon the nanoscale but relatively slow (min/h). Here, we demon-strate that DNA hybridization can be leveraged through me-chanical advantage to power rapid motion.Our basic mechanical device is an extended hinge (Fig. 1A),

which can be closed or opened by zipping or unzipping com-plementary DNA strands via applied light, heat, or mechanicalforce. It consists of two semirigid DNA origami six-helix bundles(6HBs, 410 nm long) (6, 7) joined end to end by short semi-flexible single DNA strands (ssDNA) (8). On each rod, there arecomplementary DNA sticky ends proximal (14 nm) to the hingevertex, forming a “bridging DNA zipper.” The mechanical ad-vantage, lever arm ratio, is 410/14 nm ∼30 for a single hinge.Attaching one arm to a substrate and extending the other arm totwo 6HBs makes it a trimer (Fig. 1B). With a bead attached to itsend, we have a device with a throw of 1.6 μm. We use ssDNA(two 2 nt thymine) at the hinge vertex to open it and a bridgingzipper with 16 paired nt to close it. We can open and close thehinge by cycling temperature. Fig. 1 C and D shows the beadpositions at 16 and 42 °C from optical microscopy. Global heating/cooling cycles take seconds/minutes (SI Appendix, Fig. S2). Wealso cycle trimer hinges using azobenzene-modified (9) sticky endswith 420/360 nm light to open/close the hinge (SI Appendix, Fig. S4).

For large extensions, we combine 10 rods into an “accordion,”attached to the substrate at one end and to a 500-nm colloidalbead (10–15) at the other end (Fig. 2A and SI Appendix, Fig, S5).Force-extension measurements (16, 17) on the accordion weremade by pulling on the tethered bead with optical tweezers untilthe bead escapes the optical trap (Fig. 2B and SI Appendix, Fig,S7 and Movie S1). Mechanical advantage amplifies 6 pN on thebead to ∼180 pN on DNA zippers. The total throw of the ac-cordion is 7.4 μm. The equilibrium particle position distributionand Boltzmann statistics yield the initial restoring force andequilibrium position (SI Appendix, Fig. S8). Force calibration isdetailed in SI Appendix, Fig. S6.In the force-extension curve (Fig. 2 B and C), bridging DNA

unzips in the range 8 to 20 pN or 0.27 to 0.67 pN applied to theaccordion ends. A control with no bridging DNA zippers (blue)is well fit as a freely jointed chain, Langevin function (black) (SIAppendix, Fig. S10). The force-extension curve agrees well withthe rms displacement (SI Appendix, Fig. S9) from an elasticspring model at low force and an entropic freely jointed chain atlarge force. The integrated area (shaded green) between theaccordion (red) and the control (blue), 408 kBT (±8.3%), is themeasured work done and energy stored in the unzipped DNA.By comparison, the calculated ΔG for the particular sequences

Significance

With simple DNA origami lever arms arranged in hinges andaccordion structures, we amplify the nanometer displacementsfrom DNA hairpin zippers to 4-μm motion, easily observableand quantified in real space and real time with conventionaloptical microscopy. Mechanically pulling a bead tethered onthe accordion end, we measure high-energy recovery and re-traction speeds up to 50 μm/s. On longer time scales, we havealso opened and closed the hinges with light and heat. DNAnanotechnology, and particularly DNA origami, combined withcolloids and emulsions can provide powerful architectures. Thepresent study is a step toward activating such colloidal/cellularscale devices using DNA as a power source/fuel. We envisionartificial active flagella, cilia, micropumps, and other cellularscale devices.

Author contributions: G.Z., K.B., D.G., N.S., and P.C. designed research; G.Z., M.H., R.S.,F.Z., M.Y.B.Z., Y.Z., N.S., and P.C. performed research; G.Z., R.S., D.G., N.S., and P.C. con-tributed new reagents/analytic tools; G.Z., N.S., and P.C. analyzed data; and G.Z., R.S., K.B.,D.G., N.S., and P.C. wrote the paper.

The authors declare no competing interest.

This article is a PNAS Direct Submission. O.G. is a guest editor invited by theEditorial Board.

This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND).1To whom correspondence may be addressed. Email: gz429@nyu.edu, ned.seeman@nyu.edu, or chaikin@nyu.edu.

This article contains supporting information online at https://www.pnas.org/lookup/suppl/doi:10.1073/pnas.2023508118/-/DCSupplemental.

Published May 17, 2021.

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used is 418 kBT (±5%) (18): The mechanical work done on theextension has been converted to recoverable DNA hybridizationchemical energy that can be used to move the tethered beadthrough the viscous medium.The bridging DNA zippers used in Fig. 2 have 30 nt pairs plus

4 nt spacers at midpoint and remain hybridized with at least 8 ntpairs upon complete accordion extension. Shorter zippers (21 ntpairs), which are completely unzipped at full extension, showhysteresis (Fig. 3). At large extension, the only reactive force isentropic; therefore, the completely unzipped states lie on thesame curve as the control, the freely jointed chain that lacks anybridging DNA zippers. At shorter extension, DNA zippers arepartially hybridized, exerting an enthalpic force, in addition tothe entropic force. The hinges are at least partially closed, andthe force is transmitted from one hinge to the next by the elasticbending of the 6HB rods; see SI Appendix, Fig. S3. The lossesonly arise upon completely unzipping and then renucleating thehybridization, similar to losses in forming secondary structures inRNA or proteins on folding (19, 20).To quantify the time scale for such DNA devices, we pull the

bead to near full extension and release, using the accordion withzippers long enough that they are always partially bound, andexhibit no hysteresis (Fig. 2). We use beads of two sizes, 500(blue) and 1,000 nm (red). Both show a fast pull back within afraction of second (Fig. 4B and Movie S2), with a peak velocity of50 and 25 μm/s, respectively (Fig. 4C). The time and speed de-pend on the load rather than the folding time (10 to 100 μs) ofthe DNA hairpin (21). A model including particle and accordionStokesian drag near a wall agrees with our observations (SIAppendix, Fig. S11). The force is mostly entropic at large ex-tension and mostly elastic at short distances. The extension rangein which the DNA hybridization is the dominant driver is from3,000 to 1,000 nm. The collapse in this region happens within0.1 s and at speeds exceeding 25 μm/s. Using shorter DNA zip-pers (SI Appendix, Fig. S12), it takes ∼1 s for the devices to

return to 1,000 nm, as the complementary single strands mustfirst diffuse to make contact, initiating hybridization.To show directly that the bridging DNA is indeed unzipped

upon accordion extension for short DNA zippers, we prepared aset of probe colloids coated with 21-base ssDNA, complementaryto one side of a particular DNA zipper. Probe colloids held closeto the unstretched accordion do not bind. When the accordionbead is pulled to full extension, the probe particle attaches to thedesignated open hinge strand. In three designs, with the probesprogrammed to bind to zippers at 400, 1,200 (Fig. 5A), and2,000 nm (Fig. 5B), we observe binding. The binding is confirmedby pulling the bead around a circle at maximum extension andobserving that each probe bead follows concentrically at its ap-propriate radius (SI Appendix, Fig. S13). Thus, our DNA ac-cordion also exhibits remote sensing, a simple primitive form ofmechanical allostery (22, 23), a displacement applied at one endof our construct allows binding at a distant site (Movie S3).There have been many previous experiments pulling on DNA

in clever configurations: long unhybridized sequences that exploreDNA as a prototype entropic polymer (24), hairpin structures (25)that quantify hybridization free energy calculations and explorekinetics, or beautifully designed DNA springs (26) that demon-strate efficient purely elastic behavior with no dehybridizationupon stretching. The present study builds on these studies andextends them to quantify the speed and reversibility of storing andrecovering, specifically the dehybridization energy stored on themesoscopic (many micrometers) scale.We have demonstrated that the energy associated with DNA

hybridization at the nanometer scale can be leveraged to pro-duce controlled motion at the micrometer scale, with a 1.6-μmDNA construct activated by heat or by light. Furthermore, wehave made an accordion, which demonstrates that DNA can beutilized at the ∼4-μm scale to store and reversibly recover energyon a time scale of fractions of a second, producing speeds up to50 μm/s. Unlike biological motors, in which the machine and thechemical energy storage are separate, DNA constructs incorporate

Fig. 1. Devices, hinges, accordions, and thermal cycling. (A) The basic device is made of 6HB DNA origami rods linked with a short ssDNA connection at thehinge vertex and closed by a bridging DNA zipper attached 14 nm from the vertex. (B) A simple DNA heat engine—one 6HB is attached to the substrate, andtwo rigidly connected rods attach to a bead. The DNA zippers close at 16 °C and open at 42 °C. (C) Bead positions in two full cycles of 16 to 42 °C to 16 to 42 °C.(D) The particle’s probability distribution along the x-axis in the hot and cold states. Dashed black and solid gray lines are calculated frommodels with thermalmotion and elastic restoring force (SI Appendix, Fig. S1).

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both functions in a single molecule (3). It is worth emphasizingthat in our devices we make use of reversible hydrogen bonds incontrast to the lossy use of ATP hydrolysis in molecular motors.The present system, combining mechanical advantage and shortDNA strands that hybridize without initiation and without folding

entanglements, is easily extended to even larger distances byadding more hinges (27). It has the advantage that it avoids theentanglements and distortion concomitant with folding large DNAhairpins. This system suggests a paradigm for the design of de-vices on the nanometer to cellular scales. Combined with the

Fig. 2. Force-extension curves for the accordion construct. (A) An “accordion” of 10 6HBs, with nine DNA zippers and two 4T ssDNA at the vertices. The first6HB is bound to the substrate with sticky “legs” and the last to a bead with sticky “hands.” (B) Each red point is an average over 40 measurements on each offive samples. Dashed red is calculated from the Boltzmann distribution, measured with no force. Solid blue is a control experiment with no bridging DNAzippers. Dashed blue is from the equilibrium distribution of the control. Solid black is the Langevin function for a 10-mer freely jointed chain. The greenshaded area (408 kBT) is the work done and energy stored in extending the accordion (ΔG for unzipped sequences is 418 kBT). (C) Measured and calculatedcurves to full extension.

Fig. 3. Hysteresis with complete unzipping of short DNA zippers. (A) The bead is pulled to 3,800 nm with 6 pN. Held with these forces, the extension isdecreased. The trapping force is then lowered until the accordion pulls the bead out from the trap. The force and extension are recorded (red points).Without changing the trapping force, the bead is then pulled from its equilibrium position to where it is pulled out from the trap. Force and extension arerecorded (blue points). Each trapping force corresponds to two extensions. An example is the two points just inside the dashed gray ellipse. The two statescorrespond to zipped and unzipped bridging DNA zippers, as illustrated above and below the ellipse. (B) Snapshots of the experiment for one set of pointswith green as full extension, red the position where the bead escapes the trap, yellow the equilibrium position to which the bead retracts, and blue theposition that the bead can be pulled to with the same (escape) force, ∼0.33 pN. (Scale bar, 1 μm.)

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sophistication developed over the past four decades in structuralDNA nanotechnology (28–36), our work opens the door to pro-grammable microdevices, artificial cilia, micromuscles, Escherichiacoli–like swimmers with active flagella, and remote sensors.

MethodsPreparation of the 6HB DNA Origami and Accordion.6HB DNA origami buffer. 1× Tris-acetate-EDTA buffer with 10.5 mM Mg(12.5 mM Mg, 2 mM EDTA), the annealing 6HB monomer, is created whenthe solution was ramped up to 68 °C, remained at that temperature for30 min, ramped down at 10 to 28 °C/h, left for 5 h, and then ramped at 60 °C/h down to 4 °C for retrieval.Purification.Different 6HBs are purified separately with a 100 Kd Amicon filter.A total of 200 μL 6HB was prepared with M13 (10 nM) and each staple strand(100 nM). The material was purified three times by filling the 400-μL spinfilter with buffer to its maximum volume (total ∼400 μL); the filter wascentrifuged at 2.2 k relative centrifugal force (RCF) for 12 min. Following thefinal step, the remaining material was retrieved by centrifuging the invertedfilter at 2.4 k RCF for 3 min.Annealing the accordion assembly. A total of 10 different 6HBs was mixed,ramped up to 43 °C, annealed for 5 h, ramped down to 28 °C at 0.1 °C/h, andleft for 10 h; the material was then ramped down to 4 °C at 1 °C/h forretrieval.Annealing the trimer assembly. Three different 6HBs were mixed, ramped up to43 °C, and left for 5 h. The solution was then ramped down to 28 °C at0.5 °C/h and annealed for 10 h. The solution was then ramped down to 4 °Cat 10 °C/h for retrieval.

Preparation of the DNA-coated colloidal beads follows the protocol ofref. 11.

Preparation of the Accordion–Colloid Assembly. The assembly buffer con-sists of the following: 1× phosphate-buffered saline (155 mM Na), MgCl2(10.5 mM Mg), and 0.1% F127 (wild type/wild type).Assembly. A total of 2.5 μL DNA-coated beads (100 pM) were mixed with2.5 μL 2× assembly buffer and 4 μL 1× assembly buffer, to which 1 μL DNAorigami (diluted with 1× assembly buffer to keep the ratio of origami:beads =1:5) was added. Then, 1 μL tracking reference particle was diluted (100 pM)with 1× assembly buffer to 150 μL and gently rotated for at least 4 h at roomtemperature.

Assembly of the Sample Cell. A glass coverslip (Thermo Fisher Scientific brand)and glass slide were washed with ethanol and then deionized (DI) water. Achamberwasmadewith two pieces of glass spacedwith two pieces of double-sided tape (∼120 μm thick); the sample cell is 1 to 2 cm wide, with a totalvolume of ∼20 μL. A total of 20 μL biotin-labeled bovine albumin (2 mg/mL)was added to the sample cell and annealed for 15 min before washing with1× assembly buffer (60 μL each time, three times). Then, 30 μL streptavidin(2 mg/mL) was added to the cell and annealed for 15 min before washingwith 1× assembly buffer (60 μL, seven times). The cell was then washedwith 30 μL biotin DNA (10 μM) and left for 15 min before washing with 1×

assembly buffer (60 μL, seven times). A total of 10 μL accordion–colloid as-sembly was diluted to 20 μL with the 1× assembly buffer, added to the cell,and annealed for 15 min before washing (60 μL, three times). Then, 60 μLtracking reference particle solution was added and annealed 10 min beforewashing (60 μL, eight times). Finally, the sample cell was sealed withultraviolet (UV) glue.

AFM Imaging. Bruker atomic-force microscopy, ScanAsyst, Peak Force Tap-ping in Air mode was used.

The DNA origami monomer was diluted to a concentration of 0.2 nM.Then, 3 to 5 μL was deposited on the mica surface, annealed for 5 to 10 min,washed with 100 μL DI water quickly, and dried with an air gun.

Agarose Gel Electrophoresis. Around 0.8% (wild type/wild type) agarose gelswere used. Gelswere stainedwith ethidiumand imagedwithUV (365nm) light.

Light Microscopy and Particle Tracking. Conventional inverted bright field orfluorescent microscopy was used with oil or air lenses; the Interactive DataLanguage two-dimensional, particle-tracking method follows ref. 17.

Fig. 4. Accordion folding speed. (A) Schematic of the experiment. The bead is trapped in the laser tweezers, pulled to maximum extension, and released. (B)The extension is measured from micrograph movies at 30 frames/s, averaged over 40 runs. Red/blue are for 1-μm/500-nm beads, respectively. (C) Speed versustime from the data in Fig. 4B.

Fig. 5. Allostery. Probe colloids (900 nm, green) coated with ssDNA (21 nt)complementary to one strand of a specific bridging DNA zipper do not bindto the unstretched accordion. However, when the accordion is stretched,unzipping the bridging DNA zippers, the colloids attach to their specificpositions. As seen in the superposed micrographs, when the accordion bead(red) is pulled and rotated to four different angles, the probe follows therotation at a smaller radius. Radial position of the probe bead, dashed greencircle, is 1.2 μm in A and 2 μm in B; radial position of the accordion bead,dotted red circle, is ∼3.8 μm. (Scale bar, 1 μm.)

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Holographic Optical Trapping and Video Microscopy. The holographic, optical-trapping instrument is described in ref. 36.

Data Availability. All study data are included in the article and/or supportinginformation.

ACKNOWLEDGMENTS. We thank Prof. Alexander Grosberg for stimulatingconversations; we also thank Dr. Mingxin He for discussion in particlesynthesis. This research was primarily supported by the Center for Bio-

Inspired Energy Sciences, an Energy Frontier Research Center funded by theUS Department of Energy (DOE), Office of Sciences, Basic Energy Sciences,under Award No. DE-SC0000989 (G.Z., M.Y.B.Z., Y.Z., K.B., and P.C.) forconception, design, experiments, synthesis, and analysis. Partial support isby US DOE under Grant DE-SC0007991 (P.C., N.S., and R.S.) for initiation,management, and origami preparation and characterization and the Mate-rials Research Science and Engineering Centers program of the NSF underAward No. DMR-1420073 (M.H. and D.G.) for laser tweezer construction andprogramming and for imaging analysis.

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