Newly discovered electrical activity within cells may alter how biologists think about biological chemistry.

Electrical charges play a crucial role in the human body. The majority of biological processes are dependent on electrical ions traveling across the membranes of each of our body’s cells, which send pulses of energy through the brain and nerves that resemble lightning.

These electrical signs are conceivable, to some extent, due to a lopsidedness in electrical charges that exists on one or the other side of a cell layer. Until recently, scientists believed that the membrane was a key factor in this imbalance. However, when Stanford University researchers discovered that microdroplets of water and air can have similar unbalanced electrical charges, that notion was thrown into doubt.

Now, Duke University researchers have discovered that these kinds of electric fields also exist within and around biological condensates, a different kind of cellular structure. These structures are formed by differences in density, similar to oil droplets floating in water. They create compartments within the cell without the need for a membrane’s physical boundary.

“This discovery, like the potential energy imparted on a point charge placed in an electric field, provides a plausible explanation of where the reaction energy could have come from.”

Yifan Dai, a Duke postdoctoral researcher working in the laboratory of Ashutosh Chilkoti,

The decision was made by the researchers to investigate the possibility of small biological condensates exhibiting the same electrical imbalances as water microdroplets when they interact with air or solid surfaces. Additionally, they wanted to determine whether, like these other systems, these imbalances sparked reactive oxygen, or “redox,” reactions.

Their fundamental discovery, which was published on April 28 in the journal Chem, has the potential to alter how scientists approach biological chemistry. It might also shed light on how the first life on Earth harnessed the necessary energy to emerge.

“In a prebiotic climate without proteins to catalyze responses, where might the energy come from?” asked Yifan Dai, a postdoctoral researcher at Duke who was working in the labs of Alan L. Kaganov Distinguished Professor of Biomedical Engineering Ashutosh Chilkoti and James L. Meriam Distinguished Professor of Biomedical Engineering Lingchong You.

“This revelation gives a conceivable clarification of where the response energy might have come from, similarly to the potential energy that is conferred on a point charge put in an electric field,” Dai said.

Molecular fragments that can pair up to form hydroxyl radicals, which have the chemical formula OH, can be produced when electric charges jump between materials. The resulting hydrogen peroxide (H2O2) can be detected in trace amounts when these pair up once more.

Dai stated, “However, interfaces have rarely been studied in biological regimes other than the cellular membrane, which is one of the most essential parts of biology.” Therefore, we were curious as to whether an asymmetric system also existed at the interface of biological condensates.

Biological condensates can be made by cells to either hinder or encourage the activity of particular proteins and molecules by trapping them together. Condensates are still in their infancy among researchers’ comprehension of their workings and potential applications.

The researchers were able to easily create a test bed for their theory because the Chilkoti laboratory specializes in creating synthetic versions of naturally occurring biological condensates. With the assistance of postdoctoral researcher Marco Messina, we were able to produce minuscule condensates by combining the appropriate building block formula to A dye that glows in the presence of reactive oxygen species was added to the system by the group led by Christopher J. Chang at the University of California, Berkeley.

Their instinct was correct. A solid glow appeared at the edges of the condensates when the conditions were right, indicating the existence of a previously unknown phenomenon. The Marguerite Blake Wilbur Professor of Chemistry at Stanford, Richard Zare, whose group discovered the electric behavior of water droplets, was the next person Dai spoke with. Zare began working with the group on the underlying mechanism after hearing about the new behavior in biological systems.

“My graduate student, Christian Chamberlayne, and I thought that the same physical principles might apply and promote redox chemistry, such as the formation of hydrogen peroxide molecules,” Zare stated. “Inspired by previous work on water droplets,” The significance of condensates in cell function can be deduced from these findings.

Chilkoti stated, “Most previous work on biomolecular condensates has focused on their innards.” Yifan’s discovery that biomolecular condensates appear to be redox-active everywhere suggests that condensates evolved for more than just specific biological functions; rather, they also have a crucial chemical function that is essential to cells.

Dai cites a prebiotic as an example of how powerful this ongoing reaction might be, despite the fact that the biological implications of it are unknown within our cells. Through the same fundamental chemical process, our cells’ powerhouses, or mitochondria, generate energy for all of life’s functions. However, in order for the very first functions of life to begin functioning, something had to provide energy prior to the existence of mitochondria or even the simplest of cells.

Thermal vents in the oceans or hot springs may have provided the energy, according to researchers. Others have suggested that the ocean waves’ spray caused the same redox reaction that occurs in water microdroplets.

However, why not condensates?

Dai stated, “Magic can occur when substances become tiny and the interfacial volume is enormous in comparison to their volume.” I think the ramifications mean a lot to various fields.”

More information: Yifan Dai et al, Interface of biomolecular condensates modulates redox reactions, Chem (2023). DOI: 10.1016/j.chempr.2023.04.001

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