Neurobots—xenobots with neurons—show self-organized nervous systems and enhanced behaviors, revealing new insights into how biology builds functional structures.

In 2020, researchers at Tufts University developed tiny living structures known as xenobots using frog cells. These microscopic organisms could move through water, repair themselves, and even gather loose cells to form new xenobots.

Scientists at Tufts and the Wyss Institute have now pushed this work further by introducing nerve cells into these biological machines. The upgraded versions, called neurobots, can take on different shapes and display new patterns of movement. The findings were recently published in Advanced Science.

Led by Michael Levin, Vannevar Bush Professor of Biology, and Haleh Fotowat of the Wyss Institute, the research is part of a broader effort to understand how groups of cells organize themselves into complex structures under unfamiliar conditions. This knowledge could support advances in synthetic biology and regenerative medicine. Studying neurobots may reveal the underlying rules that guide how nervous systems form, which could eventually help scientists design new biological structures or repair damaged tissues.

Building Living Systems from Frog Cells

The team began with cells taken from early embryos of the African clawed frog, Xenopus laevis. When precursor skin cells from these embryos are isolated and placed in a dish, they naturally assemble into small, round structures covered in tiny hair-like projections called cilia.

Neurobot
A neurobot stained to highlight multiciliated cells—with small tufts of hairlike cilia around the periphery of the bot—and the neuronal extensions of dendrites and axons seen in the center. Credit: Haleh Fotowat

The coordinated motion of these cilia allows xenobots, a type of biobot, to swim through water. They are entirely biological and are created without scaffolds or genetic modification. These organisms can heal themselves and survive for about 9 to 10 days using nutrients stored in the original embryonic cells. Researchers had already studied their structure and behavior and wanted to see how adding neurons would change them, especially since these systems have no evolutionary history shaping their neural organization.

Adding Neurons: Creating Neurobots

To produce neurobots, scientists inserted clusters of neural precursor cells, which later develop into neurons, into the center of forming biobots. This was done during a brief stage when the spherical structures were still developing. The implanted cells matured and extended branching structures known as axons and dendrites throughout the interior and toward the surface.

“We wanted to find out what would happen if we provided these biobots with the raw materials needed to build a nervous system,” said Levin, director of the Allen Discovery Center at Tufts. He explained that neurobots offer a new way to study how neurons organize themselves and influence movement. “This approach is different because you now have a system with a biological body that can exhibit behavior,” said Levin.

Fotowat said the work also aims to uncover the basic principles behind how nervous systems form. “I’ve tried to understand neuronal behavior in existing animals like zebrafish and how they give rise to behavior, but neurobots are about reverse engineering. Can we build a nervous system from the start? What happens if you put neurons in a completely novel context? What are the basic, innate rules for them to organize and form networks?”

Neural Activity and Structural Changes

Microscopy showed that neurons within the neurobots developed key features found in natural nervous systems, including axons and dendrites. Researchers also detected protein markers linked to synapses, where neurons communicate. Using calcium imaging, they confirmed that these neurons were electrically active and functioning within simple neural networks.

Neurobot Showing Ciliated Surface and an Internal Network of Neuronal Projections
A neurobot stained to highlight multiciliated cells—with small tufts of hairlike cilia around the periphery of the bot—and the neuronal extensions of dendrites and axons seen in the center. Credit: Haleh Fotowat

The addition of neurons led to noticeable changes. Neurobots were generally larger and more elongated than their non-neural counterparts. Their movement also became more complex. While both types could swim, neurobots were more active and displayed repeating movement patterns instead of simple paths.

To examine how neural activity influenced behavior, scientists exposed the neurobots to pentylenetetrazole, a drug known to affect brain activity and trigger seizures. The drug altered the movement of neurobots differently than it did in non-neural biobots, suggesting that the newly formed neural networks were actively shaping behavior. This result shows that even simple, self-organized neural systems can affect how these living constructs move.

Unexpected Genetic Activity and Future Possibilities

“If you’re trying to build something new with biology, we first have to learn how cells themselves solve problems,” said Fotowat.

Researchers also observed unexpected gene activity. In addition to genes linked to major brain receptors, they found activation of genes involved in visual processing, including those associated with light-sensitive cells found in eyes. This raises the possibility that neurobots could eventually respond to light.

“We don’t know, but my hypothesis is that these neurobots are up-regulating parts of the genome that could be useful for novel functions down the line,” said Levin. “If they lived longer, would they then also develop photoreceptors? It’s a fascinating question that we are actively studying.”

Reference: “Engineered Living Systems With Self-Organizing Neural Networks: From Anatomy to Behavior and Gene Expression” by Haleh Fotowat, Laurie O’Neill, Léo Pio-Lopez, Megan M. Sperry, Patrick Erickson, Tiffany Lin and Michael Levin, 20 February 2026, Advanced Science.
DOI: 10.1002/advs.202508967

This study was funded by the U.S. Department of Defense, the John Templeton Foundation, and Northpond Ventures.

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