First Nano-Sized Molecular Device Capable of Sensing and Altering Cells’ Bioelectric Fields

Conceptual drawing of the new molecular apparatus. For experiments outside the human body (in vitro), the device will nest on the cell membrane: the “reporter” molecule can detect the local electric field when activated by red light; A connected “modifier” molecule can change this electric field when activated by blue light. Credit: Katya Kadyshevskaya at USC

With only 100 atoms, electric fields can be detected and changed

USC Viterbi researchers have created the first nano-sized molecular device capable of sensing and altering a cell’s electric field, leading to new possibilities for basic research.

Bioelectricity, the current that flows between our cells, is fundamental to our ability to think, speak, and walk.

In addition, there is a growing body of evidence that recording and altering the bioelectrical fields of cells and tissues plays a vital role in wound healing and even the fight against diseases such as cancer and heart disease.

Now, for the first time, researchers at the USC Viterbi School of Engineering have created a molecular device that can do both: record and manipulate the bioelectric field around it.

The triangular-shaped device is made up of two small particles connected – much smaller than a virus and similar in diameter DNA coast.

It is an entirely new material to “read and write” in the electric field without harming neighboring cells and tissues. Each of the two molecules, attached to a short chain of carbon atoms, has its own separate function: a single molecule acts as a “sensor” or detector that measures the local electric field when triggered by red light; The second molecule, the “modifier,” generates additional electrons when exposed to blue light. Notably, each function is independently controlled by different wavelengths of light.

Although the organoid is not intended for use in humans, it will remain partially inside and outside the cell membrane for in vitro experiments.

The work, published in the Journal of Materials Chemistry C, was led by University of Southern California Viterbi professors Andrea Armani and Rehan Kapadia. The lead authors are Yingmu Zhang, a postdoctoral researcher in the Mork Department of Chemical Engineering and Materials Science. and Jinghan He, Ph.D. Candidate at the University of Southern California Department of Chemistry. Co-authors are Patrick Sarris, a postdoctoral researcher at the University of Southern California Viterbi; Hyun Ok Chae and Subrata Das, Ph.D. Candidates in Ming Hsieh Department of Electrical and Computer Engineering. Armani’s lab was responsible for creating the new organic molecule, while Kapadia’s lab played a key role in testing how efficiently the “modifier” could generate electricity when activated with light.

Because the reporter molecule can enter tissues, it has the potential to measure non-invasive electric fields, providing ultrafast, three-dimensional, high-resolution imaging of neural networks. This could play an important role for other researchers testing the effects of new drugs, or changes in conditions such as pressure and oxygen. Unlike many other previous tools, it will do so without damaging healthy cells or tissues or requiring genetic manipulation of the system.

“This multifunctional imaging agent is already compatible with current microscopes, so it will enable a wide range of researchers—from biology to neuroscience to physiology—to ask new questions and kinds of questions,” said Armani, Ray Irani Chair in Chemical Engineering and Materials Science. On biological systems and their response to different stimuli: drugs and environmental factors. The new frontiers are endless.”

In addition, the modified molecule, by changing the cells’ near electric field, can damage with single point precision, allowing future researchers to determine cascading effects across an entire network of brain cells or heart cells, for example.

“If you have a wireless network in your home, what happens if one of those nodes becomes unstable?” Armani said. “How does this affect all the other nodes in your home? Do they still work? Once we understand a biological system like the human body, we can better anticipate its response — or change its response, such as making better drugs to prevent unwanted behaviors.”

“The key thing is that we can use this for interrogation and manipulation. And we can do both with very high accuracy – in terms of space and time,” said Kapadia, Colin and Roberto Padovani’s Head of Electrical and Computer Engineering.

The key to the new organ system was the ability to eliminate “crosstalk”. How do we make these two very different molecules stick together and not interfere with each other in the manner of two scrambled radio signals? At first, Armani notes, “it wasn’t entirely clear that it would be possible.” the solution? Separate them by a long alkyl chain, which does not affect the photophysical capabilities of each.

Next steps for this new, multifunctional molecule include testing it on neurons and even bacteria. University of Southern California scientist Moh El-Naggar, a collaborator, has previously demonstrated the ability of microbial communities to transfer electrons between cells and over relatively long distances — with huge implications for biofuel harvesting.

Reference: “Multifunctional organic molecule for electric field sensing and modulation” By Yingmo Zhang, Jingan Hee, Patrick JJ Sarris, Hyun Ok Chae, Subrata Das, Rehan Kapadia and Andrea M Armani, 8 Dec 2021, Journal of Materials Chemistry C.
DOI: 10.1039 / D1TC05065F

This work was supported by the Office of Naval Research and the Army Research Office.

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