Nanosize Device Noninvasively Assesses Cell's Electric Field

A nano-size, organic molecular device that can detect and manipulate its surrounding bioelectric field opens possibilities in biophotonics, specifically in wound healing and in the fight against diseases.

The triangle-shaped device is made of two small, connected molecules that, together, are much smaller than a virus and similar in diameter to a DNA strand. A chain of carbon atoms links the two molecules, which each harness their own function.

One molecule, called the “reporter,” acts as a sensor, or detector that measures the local electric field when it is triggered by red light. The second molecule, which the researchers called the “modifier,” generates additional electrons when it is exposed to blue light.

The use of difference wavelengths to activate each function ensures that the molecules are independently controlled.

A team at the University of Southern California (USC) Viterbi School of Engineering designed the device to be capable of “reading and writing” the electric field without damaging nearby cells and tissue. According to the researchers, the work comes at a time in which evidence that recording and altering the bioelectric fields of cells and tissue plays a vital role in wound healing and even potentially fighting diseases like cancer and heart disease is on the rise.

“The key thing is that we can use this to both interrogate as well as manipulate,” said Rehan Kapadia, the Colleen and Roberto Padovani Early Career Chair in Electrical and Computer Engineering. “And we can do both things at very high resolutions — both spatially and temporally.”

A conceptual drawing of the molecular device. For experiments outside the human body (in vitro), the device would nest on the cell’s membrane. A 'reporter' molecule would detect the local electric field when activated by red light. An attached 'modifier' molecule would alter the electric field when activated by blue light. Illustration by Katya Kadyshevskaya. Courtesy of USC Viterbi School of Engineering.

Bioelectricity is defined as the current that flows between our cells. Though not intended for use in humans, the device would sit partially inside and outside the cell’s membrane for in vitro experiments. Because the “reporter” molecule can insert into tissue, it has the possibility to measure electric fields noninvasively, providing ultrafast, 3D, high-resolution imaging of neural networks. This can play a crucial role for other researchers testing the effects of new drugs, or changes in conditions such as pressure and oxygen.

Unlike other previous tools, it will do so without damaging healthy cells or tissue or requiring genetic manipulation of the system.

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

The Armani Lab created the organic molecule, whereas the Kapadia Lab helped test how efficiently the “modifier” was generating electricity when activated by light.

In addition, the “modifier“ molecule, by altering the nearby electric field of cells, can precisely damage a single point, allowing future researchers to determine the cascading effects throughout, say, an entire network of brain cells or heart cells.

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

A challenge to the work was the elimination of crosstalk; that is, how to get two very different molecules to join together and not interfere with each other in the manner of two scrambled radio signals. The solution — to separate both molecules by a long alkyl chain — avoids affecting the photophysical abilities of either molecule.

Next steps for the molecular device will involve tests on neurons and even bacteria. The researchers noted that USC scientist Moh El-Naggar, a collaborator on the current work, has demonstrated the ability of microbial communities to transfer electrons between cells and across relatively long distances. This demonstration, they said, has implications for harvesting biofuels.

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

The research was published in the Journal of Materials Chemistry C (www.doi.org/10.1039/D1TC05065F).