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

The human body relies heavily on electrical charges. Lightning pulses of energy fly through the brain and nerves, and most biological processes depend on electrical ions traveling through the membranes of every cell in our body.

These electrical signals are possible in part because of an imbalance in electrical charges that exists on either side of a cell membrane. Until recently, researchers believed that the membrane was an essential component in creating this imbalance. But that notion was turned on its head when Stanford University researchers discovered that similar unbalanced electrical charges can exist between microdroplets of water and air.

Now researchers at Duke University have discovered that these types of electric fields also exist within and around another type of cellular structure called biological condensates. Like oil droplets floating in water, these structures are created due to differences in density. They form compartments within the cell without needing the physical boundary of a membrane.

Inspired by previous research showing that micro-droplets of water interacting with air or solid surfaces create tiny electrical imbalances, the researchers decided to check whether the same is true for small biological condensates. They also wanted to see if these imbalances trigger reactive oxygen, “redox” reactions like these other systems.

Appears in the magazine on April 28th chem, their fundamental discovery could change the way researchers think about biological chemistry. It could also provide a clue as to how early life on Earth used the energy needed to form.

“In a prebiotic environment without enzymes to catalyze reactions, where would the energy come from?” asked 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.

“This discovery provides a plausible explanation for where the reaction energy might come from, as well as the potential energy imparted to a point charge placed in an electric field,” Dai said.

When electric charges jump from one material to another, they can create molecular fragments that can pair up and form hydroxyl radicals, which have the chemical formula OH. These can then pair back up to form hydrogen peroxide (H2O2) in tiny but detectable amounts.

“But interfaces have rarely been studied in biological regimes other than the cell membrane, which is one of the most important parts of biology,” Dai said. “That’s why we asked ourselves what could happen at the interface of biological condensates, i.e. whether it is also an asymmetric system.”

Cells can form biological condensates to either separate or hold certain proteins and molecules together, either hindering or promoting their activity. Researchers are just beginning to understand how condensates work and what they could be used for.

Because the Chilkoti lab specializes in making synthetic versions of naturally occurring biological condensates, researchers were able to easily create a testbed for their theory. After combining the right formula of building blocks to make tiny condensates with the help of postdoctoral researcher Marco Messina in? Christopher J. Chang’s group at the University of California – Berkeley, they added a dye to the system that glows in the presence of reactive oxygen species.

Your guess was correct. If the environmental conditions were right, a solid glow began at the edges of the condensates, confirming that a previously unknown phenomenon was at work. Next, Dai spoke with Richard Zare, Marguerite Blake Wilbur Professor of Chemistry at Stanford, whose group determined the electrical behavior of water droplets. Zare was excited to hear about the new behavior in biological systems and began working with the group on the underlying mechanism.

“Inspired by previous work on water droplets, my graduate student Christian Chamberlayne and I thought that the same physical principles could be applied to redox chemistry and promoted, such as the formation of hydrogen peroxide molecules,” Zare said. “These results indicate why condensates are so important for cell function.”

“Most previous work on biomolecular condensates has focused on their innards,” said Chilkoti. “Yifan’s discovery that biomolecular condensates appear to be universally redox-active suggests that condensates have not simply evolved to perform specific biological functions, as is commonly believed, but that they are also endowed with a critical chemical function relevant to cells is essential.”

While the biological effects of this ongoing response in our cells are unknown, Dai points to a prebiotic example that shows just how powerful its effects could be. Our cells’ powerhouses, called mitochondria, generate energy for all of our life functions through the same basic chemical process. But before there were mitochondria, or even the simplest of cells, something had to provide energy for the very first life function to start working.

Researchers have suggested that the energy was provided by thermal springs in the oceans, or hot springs. Others have suggested that the same redox reaction that occurs in water microdroplets was generated by the spray from ocean waves.

But why not condensates instead?

“Magic can happen when substances become tiny and the interfacial volume becomes enormous compared to its volume,” Dai said. “I think the impact is important for a lot of different areas.”