There is mounting evidence that electricity is important in biology, not only within individual cells but also between them. Recent research has shown that cells can communicate with one another by sending electrical signals, implying that there is a previously unknown intercellular electricity that powers biology.
Electrical fields and activity that exist through a cell’s membrane have been discovered to exist within and around another type of cellular structure known as biological condensates. These structures, like oil droplets floating in water, exist due to density differences. Their fundamental discovery has the potential to change the way biologists think about biological chemistry. It could also reveal how the first life on Earth harnessed the energy required to survive.
The human body is heavily reliant on electrical charges. Lightning-like energy pulses travel through the brain and nerves, and the majority of biological processes rely on electrical ions traveling across the membranes of each cell in our body.
These electrical signals are made possible in part by an imbalance of electrical charges on either side of a cellular membrane. Until recently, scientists believed the membrane was a critical component in causing this imbalance. That notion was turned on its head when Stanford University researchers discovered that similar imbalanced electrical charges can exist between microdroplets of water and air.
This discovery provides a plausible explanation for where the reaction energy could have come from, just as the potential energy imparted on a point charge placed in an electric field. However, interfaces have rarely been studied in biological regimes other than the cellular membrane, which is one of the most important parts of biology.
Yifan Dai
Duke University researchers have discovered that these types of electric fields exist within and around another type of cellular structure known as biological condensates. These structures, like oil droplets floating in water, exist due to density differences. They form compartments within the cell without the physical barrier of a membrane.
Inspired by previous research demonstrating that microdroplets of water interacting with air or solid surfaces produce tiny electrical imbalances, the researchers decided to investigate whether the same was true for small biological condensates. They also wanted to see if these imbalances triggered reactive oxygen, or “redox,” reactions in the same way that these other systems did.
Appearing in the journal Chem, their foundational discovery could change the way researchers think about biological chemistry. It could also provide a clue as to how the first life on Earth harnessed the energy needed to arise.
“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 laboratory 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 could have come from, just as the potential energy imparted on a point charge placed in an electric field,” Dai said.
When electric charges jump from one material to another, they can produce molecular fragments that can combine to form hydroxyl radicals, which have the chemical formula OH. These can then combine to form hydrogen peroxide in trace amounts.
“However, interfaces have rarely been studied in biological regimes other than the cellular membrane, which is one of the most important parts of biology,” Dai explained. “So we were wondering what might be happening at the interface of biological condensates, that is, if it is also an asymmetric system.”
Cells can form biological condensates to separate or trap specific proteins and molecules, thereby inhibiting or promoting their activity. Researchers are only now beginning to understand how condensates work and what applications they may have.
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. They added a dye to the system that glows in the presence of reactive oxygen species after combining the right formula of building blocks to create minuscule condensates with help from postdoctoral scholar Marco Messina in Christopher J. Chang’s group at the University of California – Berkeley.
Their hunch was right. When the environmental conditions were right, a solid glow started from the edges of the condensates, confirming that a previously unknown phenomenon was at work. Dai next talked with Richard Zare, the Marguerite Blake Wilbur Professor of Chemistry at Stanford, whose group established the electric behavior of water droplets. Zare was excited to hear about the new behavior in biological systems, and started to work with the group on the underlying mechanism.
“Inspired by previous work on water droplets, Christian Chamberlayne, my graduate student, and I thought that the same physical principles might apply and promote redox chemistry, such as the formation of hydrogen peroxide molecules,” Zare explained. “These findings suggest why condensates are so important in the functioning of cells.”
“Most previous work on biomolecular condensates has focused on their innards,” Chilkoti explained. “Yifan’s discovery that biomolecular condensates appear to be universally redox-active suggests that condensates did not simply evolve to perform specific biological functions, as is commonly assumed, but that they also have a critical chemical function that is essential to cells.”
While the biological implications of this ongoing reaction within our cells are unknown, Dai provides a prebiotic example of how powerful it could be. Our cells’ powerhouses, known as mitochondria, generate energy for all of our life’s functions using the same basic chemical process. However, before mitochondria or even the most basic of cells existed, something had to provide energy for the very first of life’s functions to begin functioning.
Researchers believe the energy came from thermal vents in the oceans or hot springs. Others have proposed that the spray of ocean waves caused the same redox reaction that occurs in water microdroplets.
