Motion DNA: Programmable Nanoscale Motion

• Motion DNA is a field where DNA serves as both a structural scaffold and a responsive element to control and observe nanoscale mechanical motion.
• The approach uses DNA origami and toehold-mediated strand displacement to achieve discrete rotary and translational steps with sub-nanometer precision.
• Integration with external stimuli like light, chemical fuels, and electric currents enables real-time, programmable actuation monitored by high-precision microscopy.

Motion DNA refers to the integration, analysis, and programmable control of mechanical motion at the single-molecule scale using DNA as both the structural scaffold and as an element responsive to a range of chemical, optical, or electronic stimuli. This domain encompasses DNA nanomachines, synthetic molecular motors in DNA origami frameworks, programmable nanoscale mechanical systems, and dynamical molecular junctions where DNA’s motion is driven or coupled to currents, fields, or coordinated chemical manipulations. Distinct from purely structural DNA nanotechnology, Motion DNA foregrounds the quantitative engineering, observation, and manipulation of discrete molecular motions and their coupling to external inputs or collective device architectures (Zhan et al., 2021, Helmi et al., 30 Apr 2025, Liu, 2021).

1. DNA Nanomachinery: Structural and Functional Principles

Recent advances leverage DNA origami to construct rigid multi-helix bundles and programmable nano-architectures with nanometer-scale positional addressability. DNA filaments (e.g. 13-helix or 23-helix bundles, typically 7–12 nm wide and ∼100 nm long) serve as foundational components (Zhan et al., 2021). Gold nanocrystals (AuNRs, AuNPs), functionalized with hundreds to thousands of thiolated DNA oligonucleotides, mediate crosslinking, mechanical connection, and optical readout. Foothold domains—discrete single-stranded DNA overhangs—are configured in geometric patterns (e.g. rows separated by 60° or 120°) to define discrete translation or rotation steps.

Assembly hierarchy proceeds via:

1. Scaffold folding plus staple and capture strand hybridization (computer-designed via caDNAno).
2. Selective sequestration (“blocking”) of certain footholds to enforce mechanical pathing.
3. Integration of metallic nanocrystals using buffer exchange protocols, often assisted by BSPP or low-pH ligation chemistries.
4. Annealing and purification to yield motion-ready complexes (Zhan et al., 2021).

The programmable nature of Watson–Crick pairing underlies the modularity and addressability of these systems, positioning DNA origami as a versatile platform for biomimetic machine design (Liu, 2021).

2. Mechanisms of Programmable and Coordinated DNA Motion

Motion in DNA-based nanosystems is predominantly driven by carefully designed toehold-mediated strand displacement reactions. Addition of “fuel” and “removal” oligonucleotides, together with “blocking” strands to control step directionality, enables cyclical actuation through pre-defined mechanical states.

Key modalities include:

• Rotational motion: Distinct filaments can be actuated independently (e.g. 120° or 60° discrete steps) or synchronously (epicyclic gear analogues).
• Translational sliding: Rack-and-pinion analogs are achieved by arranging foothold lines, enabling motion in ±14 nm or ±28 nm steps per fuel cycle.
• Joint and synchronous motion: Multi-component architectures achieve complex, coordinated pathways, interleaving discrete sliding and rotary steps, with as many as seven defined states seen in two-filament–particle hybrid systems (Zhan et al., 2021).

Each motion step is energetically downhill by ∼10–15 k_BT per displacement cycle, and is programmable solely through DNA sequence and added fuel, obviating the need for protein enzymes or external motors (Zhan et al., 2021, Liu, 2021).

3. Observation and Quantification of DNA Motion

High temporal and spatial precision in tracking DNA-based motion is enabled by fluorescence spectroscopy, plasmon-enhanced emission, and single-molecule tracking techniques.

• Distance-dependent fluorescence: Fluorophores such as ATTO 550 and ATTO 647N, grafted to specific staple strands, yield emission rates that undergo significant quenching or enhancement in proximity (<5–10 nm) to gold nanocrystals. The quantum yield modification and enhanced excitation are explicitly modeled as

$$\frac{Y_{\rm f}}{Y_{\rm f,0}} = \frac{q}{q_0} \frac{Y_{\rm exc}}{Y_{\rm exc,0}},$$

with

$$q = \frac{Y_r/Y_{r,0}}{Y_r/Y_{r,0} + Y_{\rm abs}/Y_{r,0} + (1-q_0)/q_0}$$

where $Y_r$ and $Y_{\rm abs}$ are metal-modified radiative and absorptive rates (Zhan et al., 2021).

• Temporal and kinematic resolution: Discrete photonic intensity jumps directly report stepwise mechanical events on timescales of ∼5–10 min per strand displacement. Sub-nanometer spatial resolution is achieved (∼1–2 nm), and intermediate states (“kinks”) in fluorescence traces resolve transient conformational substates.
• Summary of motion parameters:

| Mode | Angle/Step | Translation/Step | Fuel | Duration | |----------------------|------------|------------------|-------|------------| | Independent (A) | 120° | 0 | 2′+3 | 5–8 min | | Independent (B) | 60° | 0 | 5′+6 | 3–6 min | | Joint sliding | 0 | ±14, ±28 nm | Var. | 6–10 min | | Joint rotation | 60° | 0 | 3–6 | 5–9 min |

(Zhan et al., 2021)

Such high-precision in situ readout enables real-time monitoring and analysis of complex mechanical behaviors in DNA nanomachines.

4. DNA-Based Synthetic Molecular Motors and Single-Molecule Actuation

Integration of synthetic (non-proteinaceous) molecular motors into DNA origami scaffolds advances the field of Motion DNA from chemical strand-exchange drives to photon- or electron-driven actuation.

In one paradigm, an overcrowded-alkene rotary motor is covalently attached via four orthogonal DNA adapters to a DNA origami framework. The photochemical cycle of the motor, involving sequential cis–trans isomerization and thermal helix inversion (Δθ_photo = 180°, Δθ_thermal = 60°, overall Δθ_cycle = 360°), yields a photon-to-rotation efficiency η ≈ 0.5 turn/photon. Rotary steps (∼120°/photon, ∼60°/thermal) are mechanically amplified by coupling to long (∼217–280 nm) DNA lever arms bearing high-density fluorescent reporter labels, and tracked by TIRF microscopy with ∼5 nm precision per 10 ms frame (Helmi et al., 30 Apr 2025). A subset of devices exhibit robust, UV-activated, unidirectional rotation with average angular velocities ω_on ≈ 0.21 rotations/s.

Key features include:

• Site-specific, stable four-point DNA motor conjugation.
• Distinguishing actuation signatures: motion is light-dependent, shows correct step size and directionality, and is abolished in control architectures (incomplete linkages).
• Real-time, single-molecule quantification of rotary statistics, dwell-time distributions, and torque transfer (Helmi et al., 30 Apr 2025).

This framework demonstrates that “Motion DNA” provides a programmable, robust platform for integrating and dynamically tracking synthetic molecular actuators in real time.

5. Driven, Stochastic, and Non-Equilibrium Mechanical Behavior

Motion DNA systems extend to regimes where DNA’s motion is subject to non-equilibrium forces—in particular, electric fields, electronic currents, and fluctuating environments.

• Current-driven mechanical instability and spin transport: In double-stranded DNA, tunneling spin–orbit-coupled electronic currents induce voltage-dependent modifications to the mechanical potential governing DNA conformational dynamics. At sufficient bias (V_c ≈ 0.11–0.14 V), the potential becomes bistable, leading to structural instabilities (e.g., double-well formation) and pronounced feedback between mechanical motion and spin-resolved conductance (chiral-induced spin selectivity, CISS). Time-dependent Langevin dynamics and quantum-classical nonequilibrium Green’s function calculations quantify these effects and predict ∼9% enhancement in spin polarization correlated with emergent mechanical bistability (Davis et al., 24 Jul 2024).
• Non-equilibrium molecular junctions: Under finite voltage bias, DNA’s collective coordinate in a molecular junction evolves under a Keldysh-Langevin equation combining deterministic, dissipative, and stochastic electron-driven forces. Mean first-passage times quantify the voltage-dependent lifetime to denaturation. Apparent mechanical temperatures during electron transport can reach >1200 K. Notably, increasing bias can paradoxically restabilize the molecule after initial destabilization (“barrier recovery” at high V), mediated by spatially varying fluctuations (Landauer blowtorch effect) and electronic friction (Lawn et al., 10 Sep 2025).
• Thermal and stochastic driving: The addition of controlled Gaussian noise to DNA under electrophoresis in agarose gels (“noise lubricity”) produces dramatic increases (>113%) in DNA mobility compared to pure DC field. Nonlinear friction scenarios are modeled via Langevin dynamics with spatially variable barriers, revealing a crossover from Arrhenius to super-Arrhenius activated transport and highlighting the value of noise-activated escape as a general mechanism for controlling DNA locomotion (Deb et al., 2021).

6. High-Precision Measurement and Model Systems for DNA Motion

Quantitative experimental frameworks have emerged to rigorously extract mechanical parameters and conformational changes from single DNA molecules in motion.

• Tethered Particle Motion (TPM): TPM tracks the Brownian fluctuations of a microsphere tethered to a surface by a DNA molecule, offering sub-20 ms resolution for conformational transitions (Manghi et al., 2010). Analytical scaling laws accurately partition bead- and polymer-dominated regimes for the relaxation time τ and inform optimal design for dynamic TPM assays.
• Label-free quantification of bend angles: Semi-flexible DNA fragments containing designed bends (“kinks”) or protein-induced local curvature can be characterized without perturbative labels. A kinked worm-like chain model relates mean-square Brownian excursions to bend angles θ, enabling extraction of, e.g., θ=19°, for specific sequence motifs or θ≈180° for strong protein-induced bends (e.g., IHF binding) (Brunet et al., 2015).
• Dynamical barcoding in nanopores: For DNA bearing protein “barcodes,” motion through a cylindrical nanopore is analyzed with non-equilibrium tension-propagation theory and Brownian dynamics to map dwell times to spatial configuration. Two-step weighted interpolation corrects for velocity heterogeneity, restoring barcode spatial distances to nearly 100% accuracy (Seth et al., 2021).

7. Outlook: Programmability, Modularity, and Applications

Motion DNA establishes a distinct paradigm within DNA nanotechnology, characterized by:

• High modularity: Mechanical modes (sliding, rotation, gear-trains, rack-and-pinion analogs) and step sizes are encoded by staple sequence and programmable fuel design (Zhan et al., 2021, Zhan et al., 2021).
• Integration potential: Synthetic molecular motors and external field or current inputs can be seamlessly coupled into DNA architectures, allowing multi-layer, multi-component nanomachinery (Helmi et al., 30 Apr 2025, Davis et al., 24 Jul 2024).
• Real-time, high-precision monitoring: Plasmon-coupled fluorescence and TIRF microscopy permit dynamic mechanical characterization at single-molecule level with sub-nanometer, millisecond precision.
• Extension to stimuli-gated and hybrid bio-nano systems: Light-activated, electrically triggered, or multi-fuel controlled devices are feasible. Multi-filament assemblies promise collective motion and emergent functionality reminiscent of macroscopic machines.
• Biotechnological and synthetic biology prospects: Programmable DNA motion underlies applications in cargo transport, analyte sorting, single-molecule sensing, and construction of reconfigurable nanoscale assembly lines and responsive photonic materials (Liu, 2021, Zhan et al., 2021).

Systems-level understanding of friction, damping, dissipation, and noise in these devices is now possible, bridging analytic theory, simulation, and experimental readouts, and revealing DNA as not only a structural code but a basis for engineering and measuring mechanical motion with atomic-to-mesoscale control.