Emerging Intracellular Electrical Phenomena: Implications for Paradigm Shifts in Biological Chemistry Research

Summary of the article 

The human body depends on electrical charges for many biological processes, including brain activity and nerve impulses. Previously, it was believed that cellular membranes were necessary to create an electrical charge imbalance. However, recent research from Stanford University has shown that a similar electrical imbalance can exist between microdroplets of water and air. Now, researchers from Duke University have discovered that these types of electric fields also exist within and around biological condensates, a type of cellular structure. These structures form compartments inside the cell without needing the physical boundary of a membrane. The researchers discovered that when environmental conditions are right, a previously unknown phenomenon occurs in these biological condensates, which creates a redox reaction that produces tiny amounts of hydrogen peroxide. This discovery could change the way researchers think about biological chemistry and provide a clue as to how the first life on Earth harnessed the energy needed to arise. Researchers propose that this redox reaction could have been created by thermal vents in the oceans, hot springs, or spray of ocean waves, but the discovery of redox-active biological condensates could provide a new explanation. The implications of this ongoing reaction within our cells are not yet known, but the researchers believe that the implications of their discovery are important for many different fields.

Electrical charges are a major part of how the human body functions. The majority of biological activities rely on electrical ions moving across the membranes of every cell in our body, which is why the brain and nerves experience energy pulses that resemble lightning.

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 similar imbalanced electrical charges can exist between microdroplets of water and air, that notion was proven to be incorrect.

These forms of electric fields are now known to exist within and around a different kind of cellular structure known as biological condensates, according to Duke University researchers. These structures exist because 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 decided 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 wanted to see whether these imbalances triggered "redox" events involving reactive oxygen like these other systems.

Their revolutionary finding, which was published on April 28 in the journal Chem, might alter the way scientists view biological chemistry. It might also offer a hint as to how the first 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 and generate hydroxyl radicals, which have the chemical formula OH, when they jump across different materials. These can then pair up once more to create minute but discernible amounts of hydrogen peroxide (H2O2).

However, Dai highlighted, "interfaces have hardly ever been investigated in biological regimes other than the cellular membrane, which is one of the most fundamental components of biology. So, if a biological condensate interface is an asymmetric system as well, we wondered what might be happening there.

To segregate or group together specific 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 no 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 might 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 critical chemical function that is essential to cells, as opposed to simply evolving to carry out specific biological functions as is generally understood,"

Dai mentions a prebiotic as an illustration of how potent its effects might be, even if the biological implications of this continuing interaction within our cells are unknown. Mitochondria, the powerhouses of our cells, employ the same fundamental chemical process to provide energy for all of the activities necessary for life. But for the very first of life's functions to start operating, something had to provide energy before mitochondria or even the most basic of cells existed.

According to research, the energy came from hot springs or thermal vents in the water. Some people have hypothesized that the same redox reaction 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."