There is talk of a completely new way of life: A research team led by Josh Bongard from the University of Vermont has created frog cells that are less than a millimeter in size and designed by a computer.
The “Xenobots” are able to move and heal themselves. They should even be able to take a small load, such as a medication. Bongard says that they are new types of living machines: “They are neither a traditional robot nor a well-known animal species.” Instead, they are dealing with living, programmable organisms. The researchers publish their results in the journal “PNAS”.
Combination of synthetic biology and robotics
Scientists worldwide are working on changing organisms in such a way that they take on certain properties. To do this, they use genetic engineering methods such as the gene scissors CRISPR / Cas. Bioengineers also try to grow mini-organs in the laboratory, so-called organoids – for example for personalized stem cell therapies or to be able to test drugs without animal testing. However, with this method, the researchers have very little influence on the structure of the organoids and thus also on their function. With their xenobots, Bongard and his colleagues take a slightly different path, for which they combine robotics and synthetic biology.
In principle, it works like this: A computer combines a few hundred cells into different shapes, always with the goal is that the resulting cell cluster can master a task set by the researchers, such as moving specifically in one direction. For this, the scientists used two different cell types: pluripotent stem cells and precursors of heart muscle cells.
“The stem cells are mechanically static, but they have the potential to build a kind of tissue. Cardiac muscle cells, on the other hand, can pulsate and therefore have a movement component, ”said biophysicist Friedrich Simmel from the Chair for Physics of Synthetic Biosystems at the Technical University of Munich to Tagesspiegel. Based on these properties, one can consider what a material does that forms a certain shell and twitches at different points.
Evolution simulated in the computer
This “consideration” took over in the study of the Deep Green supercomputers at the University of Vermont. To do this, he used an “evolutionary algorithm” – so put the cells together randomly and then select the result that would best handle the task in the simulation. This is based on biophysical information about what individual frog cells can do.
“The computer takes the best results, changes them further and simulates how the resulting structures would behave,” explains Simmel. For example, if the small robots are to move, it makes a difference whether the contractile heart muscle cells are located outside or centrally. The researchers ran the algorithm a hundred times. The computer discarded models that did not work, but the most promising were selected so that they could be reconstructed from real cells in the laboratory.
Using tissue forceps, pieced together a tissue from individual cells
Biologist Michael Levin and microsurgery Douglas Blackiston from Tufts University near Boston performed this demanding work. They obtained the stem cells and cardiac progenitor cells from early embryos of the African clawed frog Xenopus laevis – hence the name “Xenobots” for the creatures , After they had grown and grown the stem cells, Blackiston used micro tweezers and an equally small electrode to assemble them into tissue – as closely as possible according to the blueprints that the computers had previously output. The precursors of the heart muscle cells were then embedded in these enveloping structures – the Xenobot was ready.
In the petri dish, some of the slightly more than half a millimeter grayish creatures really began to move. The embryonic energy reserves of the cells served them as fuel. According to the researchers, they would last “days or weeks” without the need for additional nutrients. However, if the scientists turned the bots over, they could no longer move, like a beetle lying helplessly on its back. “This suggests that the movement did not come about accidentally, but because of the shape they were given,” they write.
Cell clusters that transport medication
If the robots did not move as the computer predicted, the scientists had the algorithm recalculate the model. In this way, they created not only robots that slowly moved straight ahead, but also those that moved in a circle and even collected small particles – both individually and in a group. The scientists also built specimens with a hole in the middle to reduce resistance. At least in a computer simulation, such a bag could also be used to transport objects, such as medication.
The researchers were particularly astonished that the heart muscle cells were able to communicate with each other without any further action by the scientists and could thus move in a directed manner. And: The Xenobots not only kept their specified shape, they also repaired themselves after the scientists had almost broken them up. “It's something that doesn't work with conventional machines,” said Bongard. Another difference: When the life cycle of the Xenobots ends, unlike technologies made of steel, concrete or plastic, they do not leave any waste behind after use. “They are completely biodegradable,” says Bongard. “When they have done their job, there are only dead skin cells left.”
Xenobots could help to find cancer cells
He and his colleagues can introduce different applications. Xenobots could deliver drugs to specific areas in the human body or remove arteriosclerotic plaques from the inside of arteries. But they could also be helpful in removing toxic or radioactive waste, the scientists write. And with the rapid development in machine learning or 3D printing of fabrics, many more options would soon open up. They already dream of equipping the xenobots with proteins, for example, to recognize cancer cells, or have them reproduce themselves so that they could be used in the body for a long time.
Until then, the way is still a long way, says Munich biophysicist Simmel. Also because the Xenobots are currently still too big to really infiltrate them into the body. Overall, however, he describes the work of the Americans as “quite impressive”. “It shows how concepts from robotics can be combined with those from biology.” Instead of traditional electromechanical components, the scientists would have used living cells that have certain mechanical properties. Simmel doubts whether these are the first “living robots”, as the researchers write. “They consist of cells and move, but that's a very broad definition,” says the expert.
The Xenobots can, however, also be used to research fundamental questions of biology. For example: How is it actually determined how cells cooperate? The researchers hope that the bots will help understand how cells organize, process and store information.
So what distinguishes a xenobot that consists of one hundred percent frog DNA from a “real” frog.
Co-author Michael Levin also sees a parallel in it other areas. Changing complicated systems often has unexpected consequences. “If mankind is to survive in the future, we have to better understand how complex properties arise from simple rules.”