Can DNA-nanoparticle motors get up to the mark with motor proteins?

DNA-nanoparticle motors are exactly as they sound: tiny artificial motors that use the structures of DNA and RNA to propel motion by enzymatic RNA degradation. Essentially, chemical energy is converted into mechanical motion by biasing the Brownian motion. The DNA-nanoparticle motor uses the “burnt-bridge” Brownian ratchet mechanism. In this sort of movement, the motor is being propelled by the degradation (or “burning”) of the bonds (or “bridges”) it crosses along the substrate, essentially biasing its motion forward.

These nano-sized motors are highly programmable and may be designed to be used in molecular computation, diagnostics, and transport. Despite their genius, DNA-nanoparticle motors do not have the speed of their biological counterparts, the motor protein, which is where the difficulty lies. That is where researchers are available in to investigate, optimize, and rebuild a faster artificial motor using single-particle tracking experiment and geometry-based kinetic simulation.

“Natural motor proteins play essential roles in biological processes, with a speed of 10-1000 nm/s. Until now, artificial molecular motors have struggled to approach these speeds, with most conventional designs achieving lower than 1 nm/s,” said Takanori Harashima, researcher and first writer of the study.

Researchers published their work in Nature Communications on January sixteenth, 2025, featuring a proposed solution to probably the most pressing issue of speed: switching the bottleneck.

The experiment and simulation revealed that binding of RNase H is the bottleneck wherein all the process is slowed. RNase H is an enzyme involved in genome maintenance, and breaks down RNA in RNA/DNA hybrids within the motor. The slower RNase H binding occurs, the longer the pauses in motion, which is what results in a slower overall processing time. By increasing the concentration of RNase H, the speed was markedly improved, showing a decrease in pause lengths from 70 seconds to around 0.2 seconds.

Nevertheless, increasing motor speed got here at the associated fee of processivity (the variety of steps before detachment) and run-length (the space the motor travels before detachment). Researchers found that this trade-off between speed and processivity/run-length could possibly be improved by a bigger DNA/RNA hybridization rate, bringing the simulated performance closer to that of a motor protein.

The engineered motor, with redesigned DNA/RNA sequences and a 3.8-fold increase in hybridization rate, achieved a speed of 30 nm/s, 200 processivity, and a 3 μm run-length. These results show that the DNA-nanoparticle motor is now comparable to a motor protein in performance.

“Ultimately, we aim to develop artificial molecular motors that surpass natural motor proteins in performance,” said Harashima. These artificial motors may be very useful in molecular computations based on the motion of the motor, not to say their merit within the diagnosis of infections or disease-related molecules with a high sensitivity.

The experiment and simulation done on this study provide an encouraging outlook for the longer term of DNA-nanoparticle and related artificial motors and their ability to measure as much as motor proteins in addition to their applications in nanotechnology.

Takanori Harashima, Akihiro Otomo, and Ryota Iino of the Institute for Molecular Science at National Institutes of Natural Sciences and the Graduate Institute for Advanced Studies at SOKENDAI contributed to this research.

This work was supported by JSPS KAKENHI, Grants-in-Aid for Transformative Research Areas (A) (Publicly Offered Research) “Materials Science of Meso-Hierarchy” (24H01732) and “Molecular Cybernetics” (23H04434), Grant-in-Aid for Scientific Research on Modern Areas “Molecular Engine” (18H05424), Grant-in-Aid for Early-Profession Scientists (23K13645), JST ACT-X “Life and Information” (MJAX24LE), and Tsugawa foundation Research Grant for FY2023.

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