Building biology

“Living materials” study hints at a future with bioelectronic medicine

“Construction worker” cells can build synthetic structures in the body, scientists report.

Cells are the building blocks of all living organisms. Preliminary evidence suggests we can also manipulate them to build in ways that are outside their typical purview. In a new proof-of-concept study — the first of its kind — researchers succeeded in manipulating cells to do their building-bidding, with a little help from genetics.

Co-author Karl Deisseroth, a professor of bioengineering and psychiatry at Stanford University, is renowned for pioneering the development of optogenetics, a technique that uses light to manipulate the activity of nerve cells in the brain — one of the biggest breakthroughs in neuroscience in the last few decades.

Deisseroth tells Inverse that the motivation for conducting this new study was “really a very basic curiosity-driven question: Can we have specific cells work as construction workers for us and build something?”

He teamed up with his colleague at Stanford, Zhenan Bao, a professor of chemical engineering, to find out. The findings were published Thursday in the journal Science.

Ultimately, the team was able to coax neurons — which are specialized cells — into building a synthetic structure inside of a worm. Furthermore, this structure was capable of conducting electricity. This discovery is a baby step towards having bioelectronic medicine — a rapidly emerging area of interest in the medical community. Ultimately, advocates hope that bioelectronic medicine could “turn off” diseases with electricity.

Synthetic biology meets material science

To answer their motivating question — and to determine whether or not this construction could be applied in a way that is genetically targeted — the team turned to optogenetics. Optogenetics, Deisseroth explains, when boiled down, really entails delivering things in a genetically targeted way to cells.

"Can we have specific cells work as construction workers for us and build something?"

They zeroed in on building a “structure with properties” with cells — a synthetic structure that could conduct electricity.

In turn, the scientists managed to develop a polymer that is electrically functional – meaning it is conductive – called an electroactive polymer.

To do it, the research team engineered an enzyme, which, when expressed, instructed neurons that the team had targeted using genetics to synthesize and assemble these electroactive polymers on their plasma membrane.

They homed in on the brain to conduct the experiment — a particularly tricky task considering how intricate the cellular systems and networks that make up the organ are.

“These are not things we can build as human beings ourselves,” Deisseroth explains. “But biology knows how to do it.”

“Amazingly, it worked,” Deisseroth reflects. “Not only in isolated cells but also in cells in slices of the mammalian brain and also in behaving animals – in this case, the worm.”

The team successfully created conductive, synthetic structure in the worm, C. elegans.

When they successfully managed to carry it out in isolated cells – specifically, neurons – they moved onto slices of brain from rats. When that succeeded, they decided to apply the technique to actual living things — just to see what would happen.

They took worms and assembled genetically targeted electroactive polymers in vivo, and in turn, the polymers successfully grew and attached themselves to the worm’s neurons. Furthermore, the worms’ cells remained viable, despite the fact that their membrane properties underwent remodeling, and some cell-type-specific behaviors were altered.

Now that they’ve managed to build these electroactive polymer structures, the team is considering what other things they could build, and what other cell types they could turn their attention to.

“You can target multiple different kinds of cells in the same tissue and start to get really complex structures,” says Deisseroth.

Still, Deisseroth says they are not ready to translate the findings to applications in humans any time soon. “You can't rule anything out, given how fast things move,” he says. “But our main goal is to get this as a platform for exploration,”

But he says the question of what’s next for this line of research hangs wide open: “We're actually curious to see where it leads us.”

Abstract: The structural and functional complexity of multicellular biological systems, such as the brain, are beyond the reach of human design or assembly capabilities. Cells in living organisms may be recruited to construct synthetic materials or structures if treated as anatomically defined compartments for specific chemistry, harnessing biology for the assembly of complex functional structures. By integrating engineered-enzyme targeting and polymer chemistry, we genetically instructed specific living neurons to guide chemical synthesis of electrically functional (conductive or insulating) polymers at the plasma membrane. Electrophysiological and behavioral analyses confirmed that rationally designed, genetically targeted assembly of functional polymers not only preserved neuronal viability but also achieved remodeling of membrane properties and modulated cell type–specific behaviors in freely moving animals. This approach may enable the creation of diverse, complex, and functional structures and materials within living systems.
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