The motive forces in DNA-enabled nanomachinery

Abstract

Building machines that can augment or replace human efforts to accomplish complex tasks is one of central topics for humanity. Especially, nanomachines made of discrete numbers of molecular components can perform intended mechanical movements in a predetermined manner. Utilizing free energies of Watson-Crick base pairing, different types of DNA nanomachines have been invented to operate intended stepwise or autonomous actions with external stimuli, and we here summarized the motive forces that drive DNA-based nanomachineries. DNA tweezers, DNA origami actuators, DNA walkers, and DNA machine-enabled bulk sensing are discussed including structural motif design, toehold creations for strands displacement reactions, and other input forces, as well as examples of biological motor-driven hybrid nanomachines. By addressing these prototypical artificial nanodevices, we envision future focuses should include developing various input energies, host cell-assisted structure self-replication, and nonequilibrium transportations.

Keywords: Biochemistry; Supramolecular chemistry.

Graphical abstract

Figure 1

Bicycle and ATPase as macroscopic man-made machine and the smallest biomolecular motor, respectively (A) Bicycle converts the inputted man power to the rotation of wheels. The forces (red arrow) that pushed down on the pedals rotate the crankset (yellow arrow), generating a torque which is transmitted to the wheel through the bicycle chain (green arrow) and rear cassette (blue arrow). The forces of the wheels against the ground cause the backward forces (F_rear-F_fwd) to wheels, propelling the bicycle forward. (B) The electron-transport chain generates a proton gradient across the inner mitochondrial membrane. Protons then flow back into the matrix to equalize the distribution, creating a proton-motive force which drives the spinning movement of c-ring and the rotational catalytical phosphorylation of ADP to ATP.

Figure 2

The principal strands displacement reactions (SDRs) and SDR-enabled nanomachines (A) Schematic illustration of free-energy changes in a typical strands displacement reaction. The invader strand (red) releases the protector strand and hybridizes to the incumbent strand in an exergonic manner. (B) 2-fold strands displacement reaction design examined the mismatch positions are critical to the displacement rates. (C) Instead of mismatches, a random sequence pool was introduced to serve as the first round for strands displacement kinetics control. (D) The DNA tweezer is the pioneer DNA machine driven by DNA strands displacement reactions. The switchable movement can be monitored by fluorescence signal of FRET (fluorescence resonance energy transfer) pair dyes TET (5‘-tetrachloro-fluorescein phosphoramidite) and TAMRA (carboxy-tetramethylrhodamine) that labeled on two arms. (E) DNA origami box with lid that opened or closed by strands displacement reaction. (F) DNA origami-based nano-winch which can operate on cell surface via single- and double-stranded DNA linkages. (G) DNA origami-based nanoprinter using three independent DNA origami linear actuators can position the write head over a two-dimensional canvas driven by strands displacement reactions. Figure 2B and 2F reproduced from Haley et al. and Mills et al. that are open-access articles distributed under the terms of the Creative Commons CC BY license; Figure 2C and 2G are adapted with permission from Mayer et al., copyright ©2023 American Chemical Society and Benson et al., copyright ©2022 The American Association for the Advancement of Science, respectively.

Figure 3

Triplex formation and base pair stacking enabled nanomachines (A) Two pyrimidine and one purine triad TA∗T and CG∗C formed through the combination of Watson-Crick and Hoogsteen interactions. (B) Reversibly opened and closed origami nanocapsule using pH-responsive triplex DNA motif. (C) Triplex DNA-enabled configurable DNA origami lattices that are responsive to pH. (D) Hoogsteen triplex origami structures (up: the design principle; down: left is formed via parallel triplex design and right is via nonparallel triplex design). (E) Schematic illustration of the free-energy changes with/without one extra base pair stacking interaction (left) and the corresponding super-resolution data (right). The cyan and magenta docking strands are for identifying the origami location and for analyzing base-stacking interactions, respectively. (F) Base pair stacking-enabled origami assembly in one-dimensional array. (G) Switchable shape-complementary DNA objects in open and close conformations that are responsive to temperature. Figure 3B (Ijäs et al., copyright © 2019 American Chemical Society), 3C (Julin et al., copyright © 2023 The Authors; Published by American Chemical Society), and 3E (Banerjee et al.²⁸) are reproduced from articles that licensed under CC-BY. Figure 3D and 3G are adapted with permission from Ng eta al., copyright ©John Wiley and Sons and Gerling et al. copyright ©The American Association for the Advancement of Science, repectively.

Figure 4

B-Z transition, entropic forces, and intramolecular secondary structure enabled nanomachines (A) B-Z transition investigated by fast atomic force microscopy by labeling B-Z transition flag inside an origami frame. (B) Force clamp based on entropic elasticity of single-stranded DNA (ssDNA) spring. On a given DNA origami rigid supporter, the longer the ssDNA, the higher entropy and the lower entropic force. (C) Assembling macroscopic machine design, DNA origami technique can assemble angular, linear motion, and crank-slider mechanism at nanoscale. (D) Different ssDNA spring can bend DNA origami compliant nanostructures to different angles. The shorter connection, the larger bending angles. (E) dsDNA-to-ssDNA transition created a strong contractive force which was employed to bend a DNA origami switch. (F) Two silver nanoparticles labeled at the ends of DNA arms. The closed state of DNA tweezer induced the proximity of sliver nanoparticles which further triggers surface-enhanced Raman scattering (SERS) biosensing applications. (G) Induced size changes of one-layer DNA origami upon the actuation of i-motif. (H) DNA tweezer controlled distances of cascade enzymes glucose oxidase (GOx) and horseradish peroxidase (HRP), regulating cascade reactions efficiencies. (I) An i-motif interconnected DNA tweezer on cell surfaces for real-time imaging of cell surface pH changes. Figure 4A, 4D, 4F, 4G, and 4I are reproduced with permission from previous studies^,,,, copyright © 2012, 2013, 2020, 2017, and 2018 American Chemical Society, respectively; Figure 4H is adapted with permission from Xin et al., copyright © 2013, John Wiley and Sons; Figure 4B and 4E are reproduced from Kramm et al. and Gür et al. that are open-access articles distributed under the terms of the Creative Commons CC BY license, repectively.

Figure 5

Enzyme, DNA aptamer, and non-DNA interactions enabled DNA machines and superstructures (A) DNA strands produced from telomerase reactions as fuel to close the classic DNA tweezer for monitoring human telomerase activities. (B) DNA aptamer enabled logic-gated nanorobot that in response to target antigen keys. (C) Cholesterol molecules placed on one side of single layered DNA origami introduced hydrophobic interactions to fold up the DNA origami. The addition of surfactant Tween 80 neutralizes the hydrophobic effect and opened the origami bilayer. (D) Thermo-responsive poly(N-iso-propylacrylamide) (PNIPAM) possesses hydrophilic-to-hydrophobic phases transition and enabled switchable close-open of DNA origami tweezer. (E) Employing asymmetric sequence design for binding gold nanoparticles, higher temperature can release gold nanoparticles from the lower affinity bottom arm, hence realizing thermal actuation design. (F) DNA origami polymerization based on adamantane/b-cyclodextrin host/guest interactions. (G) Dimeric origami assembly based on formation of peptide coiled-coil heterodimers. Figure 5A and 5E are reproduced with permission from Xu et al. and Johnson et al. copyright © 2018 and 2019 American Chemical Society, respectively; Figure 5B is reproduced with permission from Douglas et al. Copyright © 2012 The American Association for the Advancement of Science; Figure 5C, 5D are reproduced with permission from List et al. and Turek et al. copyright WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim; Figure 5F is from Loescher et al. © 2019 The Authors, published by Wiley-VCH Verlag GmbH & Co. KGaA; Figure 5G is reproduced with permission from Jin et al. Copyright © 2019 American Chemical Society and is licensed under CC-BY.

Figure 6

Macroscopic manipulation technique light, electricity, and magnetic field powered nanomachine (A) Nanotweezers photoswitched by light irradiation. The hybridization of azobenzene-labeled lock strands to tweezer arms is controlled via UV- or visible light-enabled trans-cis isomerization. (B) With one end anchored on electrode surface, applying different bias voltage can absorb or repel the negatively charged origamis from the surface. (C) Electric field-controlled robotic arm on a DNA origami platform. (D) DNA origami base of the nanorobotic arm is fixed on surface through biotin-NeutrAvidin binding, and the electrical actuation force on the nanorobotic arm is from an interplay between Coulomb force (F_C), electrophoresis(F_ep), and electroosmotic flow(F_eo). (E) Built by attaching twisted DNA tile-tubes to magnetic beads via biotin-streptavidin coupling, free magnetic swimmer travels along with the directions of applied magnetic field. (F) Surface-anchored origami-based magnetic nanodevices and the circular movement under in-plane but different strengths magnetic fields. Figure 6A is adapted with permission from Liang et al. Copyright © 2008 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. Figure 6B and 6D are adapted with permission from Kroener et al. and Vogt et al. Copyright © 2017 & 2023 American Chemical Society, respectively; Figure 6C is adapted with permission from Kopperger et al., copyright © 2018 The American Association for the Advancement of Science; Figure 6E and 6F are reproduced with permission from Maier et al. copyright ©2016 American Chemical Society and 80 that are licensed under CC-BY, repectively.

Figure 7

DNA machines driven by biological motors Gliding assays with dyneins immobilized on surface to move DNA nanotubes. Human cytoplasmic dyneins were re-engineered to attach different DNA-binding domains, which can recognize specific sequences that were incorporated in the DNA tube design. Figure reproduced with permission from Ibusuki et al. , copyright © 2022 The American Association for the Advancement of Science.

Figure 8

DNA walkers (A) A single-stranded DNA walker moves autonomously on predefined tracks. The nicking enzyme cutting reveals the toehold of the walker body which enables branch migration and the transfer of the motor to the neighboring stator. (B) By selectively removing block strands at unique joints, DNA walker can navigate on tracks in a controllable manner. (C) The single-stranded DNA robot bearing dual toehold of same length can reach equilibrium reactions with track strands. The extended robot arm thus can carry cargo and wonder around until placing the cargo strands at goal position. Figure reproduced with permission from Thubagere et al., copyright © 2017 The American Association for the Advancement of Science. (D) Catalytic hairpin chain reaction on microparticle surfaces demonstrated that catalyst strand (red) triggered the hybridization of H2 (mars green hairpins) to the surface-immobilized H1 (gray hairpins).

Figure 9

DNA machine-enabled sensing (A) Chiral plasmonic metamolecule (CPM) with pH-responsive DNA locks. Light illumination induced merocyanine-based photoacid to release protons which promotes the triplex formation and hence the closed right-handed state of CPM. Reaction in dark reversed the reaction and multiple cycles can be realized. (B) i-motif controlled surface hydrophobicity. With one end of i-motif labeled with hydrophobic groups, the other end immobilized on gold substrate, the formed i-motif and extended duplex can bury and expose hydrophobic groups hence change surface wettability. (C) Hairpin chain reaction (HCR) is implemented in a DNA-cross-linked polyacrylamide hydrogel and the in situ HCR expands the volume to a well-defined final size Figure 9A is adapted from Ryssy et al. that is distributed under the terms of the Creative Commons CC BY license; Figure 9B and 9C are reproduced with permission from Wang et al., copyright © 2007 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim and 115, copyright © 2017, The American Association for the Advancement of Science, respectively.