Genetically manipulating cells using synthetic materials to construct artificial structures

Researchers at the Stanford School of Engineering have designed a technique for reprogramming cells to use synthetic materials, which the team provides, to create artificial structures performing functions within the body.

Genetically manipulating cells using synthetic materials to construct artificial structures

The golden color illustrates the deposition of biocompatible polymers on two genetically targeted neurons at right, sparing neighboring cells. The selective deposition of these polymers, which can be electrically insulating or conductive, makes it possible to modulate target cell properties in living tissues and animals. Blue diamond particles represent the monomers to make the polymer diffusing globally through the tissue. The technology only enables polymers to form in targeted cells. Image Credit: Ella Maru Studio and Yoon Seok Kim/Jia Liu, Deisseroth/Bao laboratories, Stanford University.

We turned cells into chemical engineers of a sort that use materials we provide to construct functional polymers that change their behaviors in specific ways.”

Karl Deisseroth, Study Co-Lead and Professor of Bioengineering and of Psychiatry and Behavioral Sciences, Stanford School of Engineering

In a paper published in the March 20th edition of the Science journal, the scientists describe the development of genetically targeted chemical assembly (GTCA) and how the new approach was helpful to build artificial structures on mammalian brain cells and on neurons in a small worm called Caenorhabditis elegans.

These artificial structures were built by using two different biocompatible materials, where each material had a different electronic property—one was an insulator and the other one was a conductor.

According to Zhenan Bao, study co-leader and professor and chair of chemical engineering, although the focus of the current experiments was mainly on brain cells or neurons, GTCA should also be applicable to other cell types.

We’ve developed a technology platform that can tap into the biochemical processes of cells throughout the body.”

Zhenan Bao, Study Co-Leader and Professor and Chair of Chemical Engineering, Stanford School of Engineering

The scientists started by genetically reprogramming the cells they intended to modify. They achieved this through established bioengineering techniques to deliver guidelines for the addition of an enzyme named APEX2 into particular neurons.

Then, the researchers soaked the worms and other experimental tissues in a solution that contained two active ingredients—a very low non-lethal dose of hydrogen peroxide and billions of molecules of the raw material they expected the cells to use for their building projects.

As a result of the contact between the hydrogen peroxide and the neurons with APEX2 enzyme, a series of chemical reactions were initiated that combined the raw-material molecules into a chain called a polymer to form a mesh-like material.

Thus, the scientists were able to knit artificial nets with insulative or conductive properties around the neurons they desired.

The polymers modified the properties of the neurons. Based on the polymer that was formed, the neurons discharged fastly or slowly. When these polymers were developed in cells of C. elegans, the creeping movements of the worms were altered in an opposite manner.

In experiments on mammalian cells, the scientists performed similar polymer-forming experiments on living slices from mouse brains, as well as on cultured neurons from rat brains. They thus verified the insulating or conducting properties of the produced polymers.

Lastly, a low-concentration hydrogen peroxide solution was injected along with millions of the raw-material molecules into the brains of live mice to confirm that these elements were not toxic when given together.

Instead of a medical application, stated Deisseroth, “what we have are tools for exploration.” However, these tools could be helpful to analyze how multiple sclerosis, due to fraying of myelin insulation around nerves, might respond when diseased cells are triggered to synthesize insulating polymers as substitutes.

Scientists can also verify whether the formation of conductive polymers on top of misfiring neurons in epilepsy or autism could alter those conditions.

In the future, the scientists intend to investigate the variants of their cell-targeted technology. GTCA can be useful in producing an extensive array of functional materials, brought about by diverse chemical signals.

We’re imagining a whole world of possibilities at this new interface of chemistry and biology.”

Karl Deisseroth, Study Co-Lead and Professor of Bioengineering and of Psychiatry and Behavioral Sciences, Stanford School of Engineering

Source:
Journal reference:

Liu, J., et al. (2020) Genetically targeted chemical assembly of functional materials in living cells, tissues, and animals. Science. doi.org/10.1126/science.aay4866.

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