Newly discovered electrical activity within cells could change the way researchers think about biological chemistry

Electrical charges are widely utilized by the human body. The brain and nerves experience energy bursts akin to lightning, and the majority of biological functions rely on electrical ions moving across the membranes of each cell in our body.

An imbalance in electrical charges on each side of a cellular membrane makes these electrical messages conceivable in part. Up until recently, scientists thought the membrane was crucial to causing this imbalance. But when Stanford University researchers found that identical uneven electrical charges may occur between microdroplets of water and air, that notion was proven to be incorrect.

These forms of electric fields are now known to occur within and around a different kind of cellular structure known as biological condensates, according to Duke University researchers. These formations occur due of variations in density, much like oil droplets floating in water. They create compartments within the cell without a membrane's physical border.

The researchers sought to explore if small biological condensates behaved similarly to microdroplets of water interacting with air or solid surfaces, as had been shown in earlier study. They also sought to see whether these imbalances triggered "redox" events involving reactive oxygen like these other systems.

Their groundbreaking finding, which was published on April 28 in the journal Chem, could alter the way scientists see biological chemistry. It could also offer a hint as to how the earliest life on Earth managed to gather the energy required for its emergence.

Yifan Dai, a Duke postdoctoral researcher working in the lab of Ashutosh Chilkoti, the Alan L. Kaganov Distinguished Professor of Biomedical Engineering, and Lingchong You, the James L. Meriam Distinguished Professor of Biomedical Engineering, posed the question, "In a prebiotic environment without enzymes to catalyze reactions, where would the energy come from?"

"This discovery provides a plausible explanation of where the reaction energy could have come from, just as the potential energy that is imparted on a point charge placed in an electric field," added Dai.

Electric charges can create molecular fragments that can link together to generate hydroxyl radicals, which have the chemical formula OH, when they hop across different materials. These can then link together once again to create minute but discernible quantities of hydrogen peroxide (H2O2).

The cellular membrane, one of the most crucial components of life, is the only biological regime in which interfaces have been examined often, according to Dai. So, if a biological condensate interface is an asymmetric system as well, we wondered what may be occurring there.

To segregate or group together certain proteins and molecules, cells can form biological condensates, which can either restrict or enhance the function of those molecules and proteins. Condensates' functioning and potential applications are just now becoming fully understood by researchers.

The researchers had little trouble developing a test bed for their hypothesis because the Chilkoti laboratory specialized in producing synthetic variations of naturally occurring biological condensates. With assistance from postdoctoral researcher Marco Messina in Christopher J. Chang's lab at the University of California—Berkeley, they assembled the proper formula of building blocks to produce minute condensates, and then they added a dye to the system that lights in the presence of reactive oxygen species.

Their instinct was correct. The presence of a hitherto unidentified phenomena was confirmed when a solid glow first appeared from the condensates' edges under the correct environmental circumstances. The Marguerite Blake Wilbur Professor of Chemistry at Stanford, Richard Zare, whose team discovered the electric behavior of water droplets, was the second person Dai spoke with. As soon as she learned about the novel behavior in biological systems, Zare began working on the underlying mechanism with the group.

My graduate student, Christian Chamberlayne, and I reasoned that the same physical principles may apply and encourage redox chemistry, such as the creation of hydrogen peroxide molecules, as a result of earlier work on water droplets. These results point to the significance of condensates in cellular function.

The majority of earlier research on biomolecular condensates, according to Chilkoti, has been on their interiors. "Yifan's finding that biomolecular condensates seem to be universally redox-active suggests that condensates are endowed with a critical chemical function that is essential to cells, rather than simply evolving to carry out specific biological functions as is commonly understood."

Dai mentions a prebiotic as an illustration of how potent its effects may be, even if the biological consequences of this continuing interaction within our cells are unknown. The mitochondria, or "powerhouses," of our cells employ the same fundamental chemical mechanism to provide energy for every activity necessary for life. But for the very earliest of life's activities to start operating, something had to generate energy before mitochondria or even the most basic of cells formed.

According to research, the energy came from hot springs or thermal vents in the water. Some people have hypothesized that the same redox process that takes place in water microdroplets was initiated by the spray of the waves.

Why then, not condensates?

"Magic can happen when substances get tiny and the interfacial volume becomes enormous compared to its volume," stated Dai. "I believe the implications are significant to numerous fields."