The second generation of xenobots
Frog cells have become micro robots
Vera Sysoeva, N+1
Biologists have improved micro robots from Xenopus laevis frog cells. Xenobots learned to move around the site, turn in mazes, memorize the experience of meeting with blue light and clear the site of debris by raking it into heaps, and also successfully recovered from injuries. The work was published in Science Robotics (Blackiston et al., A cellular platform for the development of synthetic living machines).
Creating small robots that could move in a coordinated swarm remains a difficult task for designers: it is difficult to create and put complex programs into very small devices to control such behavior. Synthetic biology offers an alternative solution to the problem. Small living machines can inherit some of the properties of their natural predecessors: living cells themselves have a large number of sensors and signaling pathways. There are already biochemical, biomechanical and bioelectric methods of communication and control in cells, and theoretically, when developing robots, it is possible to use them rather than invent new ones.
The creation of alternative biological systems is one of the goals of biorobotonics. Basically, the forces of engineers are aimed at designing biohybrids from synthetic skeletons and living cells or tissues. In such systems, commands are executed by muscles, for example, as in the case of a cyborg stingray made of mouse cardiomyocytes, whose movement can be controlled using light. Such a system has all the advantages of a robot – synthetic components can be easily modeled and created with high accuracy. However, synthetic components also inherit traditional disadvantages, for example, inability to regenerate. The creation of a fully biological machine would allow robots, for example, to travel in an aquatic environment, collect garbage, quickly heal from mechanical damage and respond to environmental changes. Fully biodegradable robots could take on tasks in medicine and ecology.
Engineers from Tufts University, led by Michael Levin, suggested that cells "liberated" from the rest of the body will behave not as they are programmed by the genetic program by default, but demonstrate some new properties. The authors of the work decided to create xenobots from such cells.
At the beginning of the study, scientists obtained stem cells from a frog embryo. In an artificial environment, the cells gathered into small spheres of 3026 ± 180 pieces. In four days, the cells in the spheres differentiated and turned into cells of the ciliated epithelium. The size of the fully formed spheres averaged from 487± 9 (for small spheres) and up to 602±30 (for large spheres) micrometers. The life span of the spheres was about 9-10 days, while they did not need food sources: yolk plates, which are characteristic of the tissue cells of frog embryos, provided them with the necessary resources. Growing the spheres in a nutrient medium increased their life expectancy to 90 days.
During differentiation, the cells acquired the ability to move in an aqueous solution at a speed of more than 100 micrometers per second. The movement became possible thanks to the natural cilia of the cells, which usually divert various objects from the surface of the skin of frogs. The cilia on the surface of the spheres created a flow that set the entire structure in motion. At the same time, living machines moved in different ways: some moved in a straight line, some in place in a circle, some moved forward, rotating. Scientists have found out that the nature of the movement depends on how the cilia line up on the surface of the spheres at an early stage of development. Perhaps in the future it will be possible to use this fact and control the behavior of robots.
The direction of fluid flows around the xenobot, visualized using carmine dye. Drawings from the article by Blackiston et al.
On the fifth day of the experiment, the researchers inflicted lacerations about half the diameter of the sphere on some five-day-old xenobots with surgical forceps. The machines managed to close the wounds within five minutes and then restore their spherical shape. This did not affect the survival of xenobots: all successfully reached the end of the experiment.
Micrographs of the xenobot before the injury, at the time of injury, as well as 5, 10, 15 minutes and 48 hours after the injury.
Another important property that the developers hope to endow xenobots with is the ability to store information about what happened to the machines during their lifetime. In this work, scientists introduced a matrix RNA encoding a fluorescent reporter protein into the cells of embryos at an early stage of development. This protein itself has a green fluorescence. Under the influence of blue light, the fluorophore of the protein undergoes a change, and the color of the fluorescence changes to red. Such a switch can happen to record the xenobot's experience, and information can be read using fluorescence microscopy. The system was tested on 10 xenobots, which were released on a platform with a diameter of five centimeters. On one side of the arena, 20 millimeters from the place of disembarkation of cars, a spot seven millimeters in diameter was illuminated with blue light. The xenobots were given two hours to explore the space provided to them, after which the light source was removed and the xenobots' pad was placed in darkness. Two days later, out of ten xenobots, three showed strong radiation in the red spectrum, which means they visited the area of the blue light spot.
Scientists have also tested the ability of robots to move in confined spaces. To do this, the researchers designed various arenas: from fully open to capillaries with an internal diameter of 580 nanometers. In all cases, xenobots were able to move in space, bend around turns and "pass" the entire length of the capillaries, although some of them experienced some difficulties.
Finally, the authors checked whether the robots could move in concert. On the platforms prepared for xenobots, scientists laid out silicone-coated iron oxide particles measuring 5 micrometers. For 12 hours, xenobots cleared the arena of debris, shifting it into heaps. Using a computer algorithm, the authors showed that exactly how a group of such machines will move, clearing the site, largely depends on the shape of the xenobots. Surgically giving them various forms of xenobots, it will be possible to control the process. In the future, the authors hope to learn how to control a swarm of such robots.
(A, C): Xenobots cleared the site of "garbage" by piling solid particles in heaps. (C-F): the patterns of xenobots' movement predicted by the algorithm depending on their shape.
Earlier the same team of scientists has developed an algorithm that calculates the ideal shape of such biorobots for effective forward movement. Then the authors of the work manually shaped each of the xenobots.
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