Cells Form Into Living ‘Xenobots’ on Their Own

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.

Innate Drives to Survive

One such goal that Levin and his colleagues think they have seen is known as infotaxis, a push for cells to maximize the amount of information they get from their neighbors. Cells may also seek to minimize “surprise,” the chance of encountering something unexpected. The best way to do that, Levin says, is to surround yourself with copies of yourself. Some other goals are based on pure mechanics and geometry, such as minimizing the surface area of a cluster.

The genomic programs for the pursuit of these goals, he says, are very ancient. Indeed, a reversion to something like ancestral behavior from before cells figured out how to work together may emerge in cancers—where cells adopt a potentially lethal mode of organizing themselves that sets proliferation ahead of cooperation.

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If that’s right, then the variety of body shapes and functions in natural organisms is not so much the result of specific developmental programs written into their genomes, but of tweaks to the strengths and tendencies of these single-cell behaviors, which may come from both the genome and the environment.

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.

Solé agrees with that. “One of our dreams in the study of synthetic complexity is to be able to move beyond the actual repertoire of life forms that we can see around us, and to explore alternatives,” he said. The fossil traces of simple animals that began to evolve before the Cambrian era, more than about 540 million years ago, give only the vaguest hints of how multicellularity arose through the interactions of single-celled organisms.

Xenobots maintain the integrity of their novel form. When researchers cut this one almost in half, it repaired itself.Courtesy of Douglas Blackiston and Sam Kriegman

That cells might be programmed to collectively “compute” their own ways solutions to growth and form, rather than for their genome to prescribe them, makes sense in evolutionary terms, because it means that the collective goals of the cells in a tissue remain resilient to disturbance. There’s no need to hard-wire a contingency plan into the genome for every injury or challenge the tissue might face, because the cells will spontaneously revert to the right course. “What you have is organs and tissues that have very specific large-scale goals, and if you try to deviate them off of that, they will come back,” Levin said.

This robustness against disruption seems to be borne out by the fact that the xenobots can regenerate from damage. “Once they’ve developed this new body, they have some ability to maintain it,” Levin said. In one experiment, a xenobot was cut almost in two, its ragged halves opened up like a hinge. Left to itself, the hinge shut again and the two fragments rebuilt the original shape. Such a movement requires substantial force applied at the hinge joint—a situation skin cells would not normally encounter, but which they can apparently adapt to.

Navigating Without a Map

Whether the xenobots really are on a new and distinct developmental path remains unclear at this point. Christoph Adami, a microbiologist at Michigan State University, suggests that the xenobots’ development of cilia, for example, might not reflect some novel “decision” but rather just an automatic response to the mechanical forces acting on the cell clusters. He thinks that more work, perhaps by tracking changes in gene expression, will be required to establish what’s happening.

But Levin said that the idea of cells collectively deciding on and remembering goals is supported by experiments that he and his colleagues conducted previously on Xenopus tadpoles. To become a frog, a tadpole has to rearrange its face; the genome was thought to hard-wire a set of cell movements for every facial feature. “I had doubts about this story,” Levin said, “so we made what we call Picasso tadpoles. By manipulating the electrical signals, we made tadpoles where everything was in the wrong place. It was totally messed up, like Mr. Potato Head.”

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