DNA nanoparticle motors are exactly what they sound like: small artificial motors that use DNA and RNA structures to drive movement through enzymatic degradation of RNA. Basically, chemical energy is converted into mechanical motion by bypassing Brownian motion. The DNA nanoparticle motor uses the “burned bridge” Brownian ratchet mechanism. In this type of movement, the motor is driven by breaking down (or “burning”) the bonds (or “bridges”) it crosses along the substrate, essentially diverting its forward motion.
These nanometer-sized motors are highly programmable and can be designed for use in molecular computing, diagnostics, and transportation. Despite their genius, DNA nanoparticle motors don’t have the speed of their biological counterparts, the motor protein, which is where the problem lies. This is where researchers come in to analyze, optimize, and reconstruct a faster artificial motor using a single-particle tracking experiment and geometry-based kinetic simulation.
“Natural motor proteins play essential roles in biological processes, with speeds of 10 to 1,000 nm/s. Until now, artificial molecular motors have had difficulty approaching these speeds, with most conventional designs achieving less than 1 nm/s,” Takanori said. Harashima, researcher and first author of the study.
The researchers published their work in Nature Communications on January 16, 2025, presenting a proposed solution to the most pressing speed problem: changing the bottleneck.
The experiment and simulation revealed that RNase H binding is the bottleneck that slows down the entire process. RNase H is an enzyme involved in genome maintenance and breaks down RNA into RNA/DNA hybrids in the motor. The slower RNase H binding occurs, the longer the pauses in movement, leading to a slower overall processing time. By increasing the concentration of RNase H, the speed was markedly improved, showing a decrease in pause duration from 70 seconds to around 0.2 seconds.
However, the increase in motor speed came at the cost of processivity (the number of steps before detachment) and stroke length (the distance the motor travels before detachment). The researchers found that this trade-off between speed and processivity/execution length could be improved by a higher rate of DNA/RNA hybridization, bringing the simulated performance closer to that of a motor protein.
The designed motor, with redesigned DNA/RNA sequences and a 3.8-fold increase in hybridization rate, achieved a speed of 30 nm/s, a processivity of 200, and a stroke length of 3 μm. These results demonstrate that the DNA nanoparticle motor is now comparable in performance to that of a motor protein.
“Ultimately, our goal is to develop artificial molecular motors that outperform natural motor proteins,” Harashima said. These artificial motors can be very useful in molecular calculations based on motor movement, not to mention their merit in diagnosing infections or disease-related molecules with high sensitivity.
The experiment and simulation performed in this study provide an encouraging outlook for the future of DNA nanoparticles and related artificial motors and their ability to be compared with motor proteins, as well as their applications in nanotechnology.
Takanori Harashima, Akihiro Otomo, and Ryota Iino of the Institute of Molecular Sciences of the National Institutes of Natural Sciences and the Graduate Institute of Advanced Studies of SOKENDAI contributed to this research.
This work was supported by JSPS KAKENHI, Grants for Areas of Transformative Research (A) (Publicly Offered Research) “Mesohierarchy Materials Science” (24H01732) and “Molecular Cybernetics” (23H04434), Grant for Scientific Research in Innovative Areas “Molecular Engine” (18H05424), grant for early career scientists (23K13645), JST ACT-X “Life and Information” (MJAX24LE), and Tsugawa Foundation FY2023 Research Grant.