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How DNA molecules and enzymes can control robot swarms

In a development that brings us closer to swarms of autonomous molecular robots, Japanese researchers have developed a DNA-based molecular controller that can control their assembly and disassembly.

A recent study published in Scientific advancesby scientists from Tohoku and Kyoto Universities, describes this new technology that has applications in nanotechnology and medicine. The robots can help diagnose and treat diseases and work both inside and outside the human body.

The molecular controller consists of artificially created DNA molecules and enzymes and can control molecular robots by outputting specific DNA molecules. As the study’s co-author, Professor of Molecular Robotics Shin-ichiro M. Nomura of Tohoku University’s Graduate School of Engineering, explains in a press release, this approach allows the robots to automatically assemble and disassemble themselves, “without external manipulation is required.” .”

This is significant because such operation allows the robots to perform tasks in environments where external signals cannot penetrate. Previous research by Professor Kakugo and colleagues presented molecular robots that move individually, while the molecular controller enables swarm-like behavior thanks to a programmed sequence.

Self-organizing and disassembling swarm molecular robots through DNA molecular controller program. Source: Shin Nomura et al.

How does it work?

As the researchers explain in the introduction to their work: “Living organisms are autonomous systems that are able to sense their environment, process information and carry out the necessary actions.” Scientists are fascinated by this autonomy and are trying to create autonomous systems synthesize that do not require manual intervention.

For engineers in the emerging field of bioinspired robotics, an emphasis has emerged on the use of both hard and soft materials. As scientists have been able to dramatically miniaturize bio-inspired soft materials, molecular robotics has evolved and attempts to create robots from molecular ingredients. “Biomolecules such as nucleic acids and proteins are promising building block candidates for molecular robots due to their programmability and high specificity,” write the scientists.

The molecular controller they developed can send a DNA signal to microtubules in a solution that serves as a command to “assemble.” The microtubules – narrow, tube-like structures that support the shape of a plant or animal cell and play an important role in essential processes such as transport and cell division – have modified DNA and are driven by molecular kinesin motors. Kinesin is a motor protein that moves along microtubules and is an important component of intracellular transport, cell division, and cytoskeletal dynamics. Once the microtubules receive the DNA signal from the controller, they can change the direction of their movement and automatically assemble into a bundled structure.

If the controller issued a “disassemble” command, the microtubule bundles would be disassembled. This is achieved by controlling the molecular circuitry that processes such signals.

A diagram of the molecular controller that sends signals for the assembly and dismantling of molecular robots. Source: Shin Nomura et al.

Proof of concept experiment

In addition to Professor Nomura, the research team consisted of associate professors Ibuki Kawamata and Professor Akira Kakugo from the Graduate School of Science at Kyoto University and doctoral student Kohei Nishiyama from Johannes Gutenberg University Mainz.

Interesting technology reached out to Professor Nomura for more details on the team’s research. Nomura explained the importance of the molecular controller her team developed, focusing on the type of technological advances required to produce it.

As the scientist shared, their molecular controller is significant because it uses a cascade reaction of DNA molecules as a program that controls the assembly and disassembly of molecular robots, which he calls a “proof of concept experiment.”

While molecular reactions in DNA circuits tend to be viewed as static, a 2017 paper by Nomura and colleagues in Science Robotics already demonstrated the possibility of using a molecular “coupling” made from modified DNA molecules to form the shape of a molecular robot to influence.

The body of this robot consisted of a vesicle made of a lipid bilayer and an actuator made of proteins, kinesin and microtubules. It also included a clutch made from designed DNA molecules. In response to a signaling molecule consisting of sequenced DNA, the clutch transferred the force generated by the motor to the membrane. This caused the robot to constantly change shape. It was also possible to stop this shape-changing behavior by shining a light on the robot, which released the signaling molecule and released the coupling.

As Nomura wrote in our correspondence, “We have shown that even dynamic targets that move quickly and powerfully can be controlled with molecular motors,” adding that they have also “gained confidence as researchers by discovering that the DNA program of the self-reinforcement system can work if it is mixed into the solution on site, rather than isolated in a CPU case that is packaged untouchable.”

What’s next for this technology?

Further development of this technology will likely lead to more complex self-controlled molecular systems, where robots tackle tasks that can only be completed as a swarm. They gathered based on a given order, carried out the tasks, and then disbanded.

The researchers see the potential for further automation of molecular robot swarms and the way they process bimolecular information by leveraging controller functionality with complex DNA circuits and amplification devices.

As Professor Nomura explained to Interesting Engineering, what’s exciting about the molecules is that while they are “designed to flicker due to entropy effects,” they can also be “ordered to move away (even temporarily).”

The possible applications of this work are numerous. In medicine, the technology can be used for targeted drug delivery and very precise surgery at the molecular level. In environmental science, molecular robot swarms could help detect and neutralize pollutants. In materials science, however, the technology can help develop new materials with self-organizing properties. “The versatility of the molecular controller opens up numerous possibilities for its application in different areas,” explained Namura.

Fluorescence microscopy of molecular swarm robots that automatically assemble and disassemble. Source: Shin Nomura et al.

What’s next for the team?

As the researcher explained, they are currently focusing on some specific challenges. The main focus is on increasing the complexity and functionality of the molecular robots while maintaining very precise control.

They are also working to improve the stability and robustness of their systems in different environments. “In the future, we want to further develop the technology to come into contact with natural molecular phenomena under more stringent conditions,” said Namura, adding: “We are also exploring more real-world applications and moving from laboratory environments to practical implementations.” Specifically, this is what it is all about , to understand how this technology can be used as a “robust artificial multicellular operating system”.

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