Programmable shape-shifting molecular robots respond to DNA signals

Could function like living organisms in the near future, programmed by DNA computers
March 3, 2017

Japanese researchers have developed an amoeba-like shape-changing molecular robot — assembled from biomolecules such as DNA, proteins, and lipids — that could act as a programmable and controllable robot for treating live culturing cells or monitoring environmental pollution, for example.

This the first time a molecular robotic system can recognize signals and control its shape-changing function, and their molecular robots could in the near future function in a way similar to living organisms, according to the researchers.

Developed by a research group at Tohoku University and Japan Advanced Institute of Science and Technology, the molecular robot integrates molecular machines within an artificial cell membrane and is about one micrometer in diameter — similar in size to human cells. It can start and stop its shape-changing function in response to a specific DNA signal.

Schematic diagram of the molecular robot. (A) In response to a start-stop DNA signal, molecular actuators (microtubules) inside the robot change the shape of the artificial cell membrane (liposome), controlled by a “molecular clutch” that transmits the force from the actuator (kinesin proteins, shown in green, assemble DNA to the cell membrane when activated). (B) Microscopy images of molecular robots. When the input DNA signal is “stop,” the clutch is turned “OFF,” deactivating the shape-changing behavior. The shape-changing is activated when the the clutch is turned “ON.” Scale bar: 20 μm. The white arrow indicates the molecular actuator part that transforms the shape of the membrane. (credit: Yusuke Sato)

The movement force is generated by molecular actuators (microtubules) controlled by a molecular clutch (composed of DNA and kinesin — a “walker” that carries molecules along microtubules in the body). The shape of the robot’s body (artificial cell membrane, or liposome — a vesicle made from a lipid bilayer) is changed (from static to active) by the actuator, triggered by specific DNA signals activated by UV irradiation.

Kinesin motor protein “walking” along microtubule filament (credit: Jzp706/CC)

The realization of a molecular robot whose components are designed at a molecular level and that can function in a small and complicated environment, such as the human body, is expected to significantly expand the possibilities of robotics engineering, according to the researchers.*

“With more than 20 chemicals at varying concentrations, it took us a year and a half to establish good conditions for working our molecular robots,” says Associate Professor Shin-ichiro Nomura at Tohoku University’s Graduate School of Engineering, who led the study. “It was exciting to see the robot shape-changing motion through the microscope. It meant our designed DNA clutch worked perfectly, despite the complex conditions inside the robot.”

Programmable by DNA computing devices

The research results were published in an open-access paper in Science Robotics on March 1, 2017.

The authors say that “combining other molecular devices would lead to the realization of a molecular robot with advanced functions. For example, artificial nanopores, such as an artificial channel composed of DNA, could be used to sense signal molecules in the surrounding environments through the channel.

“In addition, the behavior of a molecular robot could be programmed by DNA computing devices, such as judging the condition of environments. These implementations could allow for the development of molecular robots capable of chemotaxis [movement in a direction corresponding to a gradient of increasing or decreasing concentration of a particular substance], [similar to] white blood cells, and beyond.”

The research was supported by the JSPS KAKENHI, AMED-CREST and Tohoku University-DIARE.

* In the current design, “there are still limitations in the functions of the robot. For example, the switching of robot behavior is not reversible. The shape change is not directional and as yet not possible for complex tasks, for example, locomotion. However, to the best of our knowledge, this is the first implementation of a molecular robot that can control its shape-changing behavior in response to specific signal molecules.” — Yusuke Sato et al./Science Robotics

Abstract of Micrometer-sized molecular robot changes its shape in response to signal molecules

Rapid progress in nanoscale bioengineering has allowed for the design of biomolecular devices that act as sensors, actuators, and even logic circuits. Realization of micrometer-sized robots assembled from these components is one of the ultimate goals of bioinspired robotics. We constructed an amoeba-like molecular robot that can express continuous shape change in response to specific signal molecules. The robot is composed of a body, an actuator, and an actuator-controlling device (clutch). The body is a vesicle made from a lipid bilayer, and the actuator consists of proteins, kinesin, and microtubules. We made the clutch using designed DNA molecules. It transmits the force generated by the motor to the membrane, in response to a signal molecule composed of another sequence-designed DNA with chemical modifications. When the clutch was engaged, the robot exhibited continuous shape change. After the robot was illuminated with light to trigger the release of the signal molecule, the clutch was disengaged, and consequently, the shape-changing behavior was successfully terminated. In addition, the reverse process—that is, initiation of shape change by input of a signal—was also demonstrated. These results show that the components of the robot were consistently integrated into a functional system. We expect that this study can provide a platform to build increasingly complex and functional molecular systems with controllable motility.