In 2020, researchers reported that they had created “biological robots” by shaping clusters of cells into small artificial forms that can “walk” on surfaces. The Levin team confirmed that these entities, called “xenobots” because they are made from skin and heart muscle cells of the African clawed frog Xenopus laevis, can be considered a new type of living organism. This claim became more convincing when researchers showed a year later that xenobots could spontaneously assemble from frog skin cells and exhibit diverse behavior while swimming in fluid.
Anthrobot Robots
The Levin team at Tufts University stated in a study published in Advanced Science that they created entities similar to robots from human cells. They are called “anthrobot robots.”
The key to making anthrobots mobile is that their surface is covered with protein cavities similar to cilia that wave and propel the structures through the fluid. To actually reach anywhere, all the cilia must move together in coordination.
Anthrobot Shapes and Behavior
Anthrobots are not only capable of swimming, but they also seem to have distinct shapes and behavioral patterns – like strains or groups within the same type of organism. The Tufts team says that anthrobots appear able to stimulate a primitive form of healing in other layers of human cells, opening up the possibility of using them in medicine.
Biological Robots as Living Beings
Some scientists suggest that the significance of human cell clusters, such as the original xenobots, is overstated; they question whether these spontaneously formed entities can truly be considered a kind of “robot.” Some argue that there is nothing particularly new or surprising about the idea that frog cells can cluster into small masses capable of movement. Jamie Davies, an evolutionary biologist at the University of Edinburgh in Scotland, who was not involved in Levin’s 2020 study or the recent one, states, “In general, the frog embryo community that knows these cells really can’t see what the fuss is about,” and considers it unsurprising that clusters of human cells might behave this way.
However, Levin says that the key here is a shift in perspective. Instead of viewing cell clusters as merely small pieces of tissue that can be used to explore human biology, we should see them as entities in their own right, with specific shapes and behaviors that can be used as a “bio-robotics platform” for medical and other applications, for example, by systematically modifying these properties to achieve beneficial behaviors such as repairing damaged tissues in the body.
Opening a Window into the Morphological Space of Human Cells
Levin states that anthrobots provide a glimpse into the “morphological space” available for human cells by demonstrating that they can automatically construct not only human body tissues and organs but also entirely different structures that did not arise from nature itself. He says, “We are exploring aspects of morphological space. Evolution gives you a small point of variation, but there’s actually so much more.” The ability of cells and tissues to develop different types of structures is referred to as “plasticity.”
Composition and Behavior of Anthrobots
Anthrobots range in size from 30 to 500 micrometers and can survive for up to two months, made from cells taken from adult human lung tissue. This tissue naturally has cilia on its surface that wave back and forth to transport mucus, which can absorb and thus remove impurities from inhaled air. (In contrast, the cilia on the frog’s skin move to transport mucus and maintain skin moisture.)
It is already known that this type of tissue can cluster into ciliated masses. Starting in the early 2010s, several research papers indicated that such aggregates, known as organoids, could be used to study lung function. In some of these papers, the cilia point inward to an empty internal space, as in branches of the human respiratory passages themselves. However, over the past few years, researchers have also found spherical cell aggregates growing with cilia pointing outward from their surface, as seen in anthrobots.
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Anthrobots and Their Behavior
The first challenge for the Tufts team was to convince others that anthrobots are independent entities in their own right, with forms and behaviors that are sought after by cell clusters collectively, rather than being somewhat random pieces of human tissue that superficially resemble microorganisms.
Although Jamie Davis, who had previously co-authored a review on synthetic morphology with Levin, has some interest in the initial work on Zenobots, he dislikes the idea that human cell clusters can “swim” with their cilia. He says it’s almost inevitable if the cilia move in harmony once the clusters are freed from the gel matrix. It’s just Newtonian mechanics and an incidental function, he adds, “I can’t see how these clusters of dancing-ciliated cells deserve to be called ‘robots’.”
Function of Organic Organs
Salvatori Simini and Gina Mokia from STEMCELL Technologies, who have also grown human airway organs, explain that the behavior of these organic organs illustrates the biological functions of the cells that compose them. If the coordinated movements of the cilia that cleanse mucus from the respiratory tracts in the organic organs are maintained with the cilia oriented outward, then the cilia will act like small paddles pushing the cell clusters through the fluid.
Levin and his colleagues assert that these movements are not just random. After statistically analyzing the movements of hundreds of anthrobots, they say that the robots appear to belong to distinct categories. In one group, the structures – small and mostly spherical – have cilia all over their surface and do not move at all. Other clusters differ in that they have irregular structures – somewhat resembling potatoes – and are only partially covered with cilia. These groups vary in the presence of cilia clustered tightly in one area, leading them to swim in circular paths, or having cilia more loosely spread out that cause them to move in straight lines.
The researchers say that all these morphological and behavioral types can be considered an implicit goal of the cell clusters – somewhat akin to types of tissues or organs in the human body.
Impact of Anthrobots on Other Cells
Levin adds, “What hasn’t been shown before is the effect of these things on other cells.” When researchers navigated the anthrobots over a flat layer of human neurons cultured on a glass substrate that had been damaged by scratching, they found that the robots helped the neurons to grow back across the gap. And this wasn’t just because the anthrobots provided a passive bridge between the edges, as small pieces of the polysaccharide gel did not have the same effect.
He says, “We don’t know the mechanism, and that’s one of the things we’re trying to figure out. But we know it’s not just a mechanical mechanism.” Levin suspects that the anthrobots are sending signals – perhaps biochemical signals – to the neurons at the edges of the scratch, encouraging them to grow into the gap.
Levin states, “Finding this capability was one of the first things we looked for. And that tells me that there are many other things that could be possible, and that this is just the tip of the iceberg. This opens up the possibility of using these structures to influence other cells [in living organisms or in a lab setting] in many other ways.” Gizem Gumuskaya contemplates researching similar healing behavior in models of human nervous system diseases, such as neuro-organs that mimic the brain; and Levin suggests that anthrobots could be used to assist in repairing damaged retinas or spinal cords. But these ideas are still mere speculations at this point.
Philip
Paul is a science writer based in London. His upcoming book, How Life Works (University of Chicago Press), will be published in Fall 2023.
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