Previously unknown intracellular electricity can power biology

(Nanowerk News) The human body is very dependent on electrical charges. Pulses of energy like lightning fly through the brain and nerves and most biological processes depend on electrical ions that cross the membranes of every cell in our body.

These electrical signals are made possible, in part, due to an imbalance of the electrical charges that exist on both sides of the cell membrane. Until recently, researchers believed that the membrane was an important component for creating this imbalance. But that thought was reversed when researchers at Stanford University discovered that a similar imbalance of electrical charges could exist between microdroplets of water and air.

Now, researchers at Duke University have discovered that this type of electric field also exists in and around another type of cellular structure called biological condensate. Like oil droplets floating in water, these structures exist because of density differences. They form compartments within the cell without requiring the physical boundaries of the membrane.

Inspired by previous research showing that microdroplets of water interacting with air or a solid surface create small electrical imbalances, the researchers decided to see if the same was true for tiny biological condensations. They also wanted to see if this imbalance triggers reactive oxygen reactions, “redox,” like these other systems. Biological condensate, like oil droplets in water, stores electrical imbalances that can provide the energy needed to start life early. (Image: Duke University)

Appears in the journal chemistry (“Biomolecular Condensate Interface Modulates Redox Reactions”), their basic discoveries could change the way researchers think about biological chemistry. It could also provide clues to how the first life on Earth harnessed the energy needed to emerge.

“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, Alan L. Kaganov Professor of Biomedical Engineering and Lingchong You, James L. Meriam Professor of Biomedical Engineering.

“This discovery provides a plausible explanation of where reaction energy comes from, just as potential energy is imparted to a point charge placed in an electric field,” said Dai.

When electrical charges jump between one material and another, they can produce molecular fragments that can pair up to form hydroxyl radicals, which have the chemical formula OH. These can then couple again to form hydrogen peroxide (H2HI2) in small but detectable amounts.

“But interfaces are rarely studied in any biological regime other than the cell membrane, which is one of the most important parts of biology,” said Dai. “So we wondered what might happen at the biological condensate interface, that is, if it is an asymmetric system as well.”

Cells can build biological condensates to dissociate or trap certain proteins and molecules, either inhibiting or enhancing their activity. Researchers are only just beginning to understand how condensate works and what it’s used for.

Because Chilkoti’s lab specializes in making synthetic versions of natural biological condensates, researchers can easily create test beds for their theories. After putting together the right building block formula to make minuscule condensate, with the help of postdoctoral scholar Marco Messina at? Christopher J. Chang’s group at the University of California – Berkeley, they added a dye to a system that glowed in the presence of reactive oxygen species.

Their hunch was right. When environmental conditions are right, a dense glow starts from the edge of the condensate, confirming that a previously unknown phenomenon is occurring. Dai next spoke with Richard Zare, the Marguerite Blake Wilbur Professor of Chemistry at Stanford, whose group established the electrical behavior of water droplets. Zare was excited to hear about the new behavior in biological systems, and started working with the group on the underlying mechanisms.

“Inspired by previous research on water droplets, my graduate student Christian Chamberlayne and I thought that the same physical principles could be applied to and promote redox chemistry, such as the formation of a hydrogen peroxide molecule,” said Zare. “These findings show why condensate is so important in cell function.”

“Most of the previous work on biomolecular condensates focused on their innards,” says Chilkoti. “Yifan’s discovery that the biomolecular condensate appears to be universally redox-active indicates that not only did the condensate evolve to perform a specific biological function as is generally understood, but that the condensate is also equipped with important chemical functions essential to cells.”

While the biological implications of these ongoing reactions in our cells are unknown, Dai provides a prebiotic example of how powerful their effects can be. The powerhouses of our cells, called mitochondria, create energy for all of our life functions through the same basic chemical processes. But before mitochondria or even the simplest cell existed, something had to provide the energy for the first life functions to get going.

Researchers have proposed that the energy is provided by thermal vents in the oceans or hot springs. Others suggest that the same redox reactions that occur in microdroplets of water are created by the bursting of ocean waves.

But why not just condensate?

“Magic can happen when matter becomes very small and the volume of the interface becomes very large compared to its volume,” said Dai. “I think the implications are important for a variety of fields.”