“Cells Form Into ‘Xenobots’ on Their Own: Embryonic Cells Can Self-Assemble into New Living Forms That Don’t Resemble the Bodies They Usually Generate, Challenging Old Ideas of What Defines an Organism”, 2021-03-31 (; similar):
Early last year, the biologist Michael Levin and his colleagues offered a glimpse of how versatile living matter can be. Levin and Douglas Blackiston, a member of his laboratory at the Allen Discovery Center of Tufts University, brought together nascent skin and muscle cells from a frog embryo and shaped the multicelled assemblies by hand. This sculpting process was guided by an algorithm developed by the computer scientists Josh Bongard and Sam Kriegman of the University of Vermont, which searched for simulated arrangements of the 2 cell types capable of organized movement. One design, for example, had 2 twitching leglike stumps on the bottom for pushing itself along.
The researchers let the cell clusters assemble in the right proportions and then used micro-manipulation tools to move or eliminate cells—essentially poking and carving them into shapes like those recommended by the algorithm. The resulting cell clusters showed the predicted ability to move over a surface in a nonrandom way.
The team dubbed these structures xenobots ( et al 2020). While the prefix was derived from the Latin name of the African clawed frogs (Xenopus laevis) that supplied the cells, it also seemed fitting because of its relation to xenos, the ancient Greek for “strange.” These were indeed strange living robots: tiny masterpieces of cell craft fashioned by human design. And they hinted at how cells might be persuaded to develop new collective goals and assume shapes totally unlike those that normally develop from an embryo.
…Some of those answers are now being unveiled in work appearing today in Science Robotics. It describes a new generation of xenobots—ones that took shape on their own, entirely without human guidance or assistance.
…The experiments described in the paper published today were remarkably simple. The same team of researchers, along with Emma Lederer of Levin’s lab, removed cells from developing frog embryos that had already specialized into epithelial cells and left them to develop in clusters on their own without the rest of the embryo, which normally provides the signals that guide cells to become the “right” type in the “right” place.
What the cells did first was unremarkable: They gathered into a ball, composed of dozens of cells or a few hundred. That kind of behavior was already well known and reflects the tendency of skin cells to make their surface area as small as possible after tissue damage, which helps wounds to heal.
Then things got weird. Frog skin is generally covered with a protective layer of mucus that keeps it moist; to ensure that the mucus covers the skin evenly, the skin cells have little hairlike protrusions called cilia, which can move and beat. We have them, too, on the lining of our lungs and respiratory tract, where their beating motion helps sweep away dirt in the mucus. But the frog skin cell clusters quickly began to use their cilia for a different purpose: to swim around by beating in coordinated waves. A midline formed on the cluster, “and the cells on one side row to the left and those on the other side row to the right, and this thing takes off. It starts zooming around”, Levin said
…Levin thinks that cells also commonly communicate electrically—that this isn’t just a property of nerve cells, although they may have specialized to make good use of it. In a xenobot, “there’s a network of calcium signaling”, Levin said—an exchange of calcium ions like that seen between neurons. “These skin cells are using the same electrical properties that you would find in the neural network of a brain.”
For example, if 3 xenobots are set spaced apart in a row, and one of them is activated by being pinched, it will emit a pulse of calcium that, within seconds, shows up in the other 2—“a chemical signal that goes through the water saying that someone just got attacked”, Levin said. He thinks that intercellular communications create a sort of code that imprints a form, and that cells can sometimes decide how to arrange themselves more or less independently of their genes. In other words, the genes provide the hardware, in the form of enzymes and regulatory circuits for controlling their production. But the genetic input doesn’t in itself specify the collective behavior of cell communities.
Instead, Levin thinks that it programs cells with an ensemble of tendencies that produce a repertoire of behaviors. Under the normal conditions of embryogenesis, those behaviors follow a certain path toward forming the organisms we know. But give the cells a very different set of circumstances, and other behaviors and new emergent shapes will appear. “What the genome provides for the cells is some mechanism that allows them to undertake goal-directed activities”, Levin said—in effect, a drive to adapt and survive.
…Jablonka guesses that the behaviors on display in the xenobots are probably “something like the most basic self-organization of a multicellular animal-cell aggregate.” That is, they are what happens when both the constraints on form and the resources and opportunities provided by the environment are minimal. “It tells you something about the physics of biological, developing multicellular systems”, she said: “how sticky animal cells interact.” For that reason, she thinks the work might hold clues to the emergence of multicellularity in evolutionary history.