Studying how cells respond to stimuli provides insight into disease mechanisms and treatment

Oregon State University scientists are deciphering how cells interact and collectively respond to chemical stimuli in the extracellular environment, knowledge that is critical to understanding physiological processes and blocking disease mechanisms.

A study by researchers from OSU’s College of Science and the Carlson College of Veterinary Medicine shows that the duration of stimuli plays a large role in the association cells‘ communication networks.

The University of Pittsburgh scientists also collaborated on what biophysicists call multicellular chemosensing, which is still shrouded in mystery despite its importance in biological processes, the researchers said.

“We are still far from fully understanding how information networks are regulated by either external stimulation or cell identity, said Guanyu Li, a doctoral student in the College of Science. – This is what our work tried to investigate.

The extracellular medium—essentially the fluid that surrounds cells—contains many types of chemicals, Lee explains. Under certain pathological or physiological conditions, the chemical composition changes and triggers a signaling process that causes cells to produce the responses necessary to maintain normal function.

Coordinated responses among a group of cells are made possible by the cells sharing molecules with their nearest neighbors, Lee said. Exchanges allow cells to sense and respond to them environmental changes in a more reliable way than if they felt and responded individually, and they allow multicellular organisms—people, animals, etc.—to survive in difficult conditions.

“For example, when you do cardio, the cells need energy, which will lead to aerobic metabolism to create a lot of ATP, an energy molecule,” he said. “When you feel thirsty, your body produces ADH—antidiuretic hormone—to reabsorb water so you don’t get dehydrated. All these changes in chemicals are like signals trying to alert the body to what is happening. The receivers of these signals are individual cells.”

By capturing or binding chemical molecules to receptors on Cell membrane, cells can detect what is happening and trigger the appropriate processes. The catch, however, is that not every cell has the same ability to bind to these molecules.

“So in any multicellular organism, coordinated sensing and responding in a group of communicating cells is really important,” Lee said.

In the study, scientists used Statistical analysis to determine the relationship of cells to their nearest neighbors, then conducted experiments to see the stimulating chemicals that affect cells and networks.

Lee, OSU Honors College student Alia Starman, and assistant professor of biophysics Bo Sun stimulated brain cells known as neurons with ATP, an energy molecule found in all life forms. In their experiments, they varied both the amount of ATP in the extracellular environment and the duration of exposure to neurons.

They also experimented with reducing the rate of cellular communication with a monounsaturated fatty acid, palmitoleic acid, and increasing it with potassium chloridemetal halide salt.

“Our analyzes show that the connectivity of the information network is mainly regulated by the temporal profile of the external stimulation — how long it lasts — and the level of communication ability of the cell itself,” Lee said. “The dose size didn’t really affect the network. It was also interesting that moderate communication skills individual cells resulted in maximum connectivity in the cell’s information network – either too much connectivity or too little both resulted in reduced network connectivity.’

The findings shed light on how the networks are regulated, opening up the possibility of controlling multicellular responses—and fighting disease—with the right stimulation of the extracellular environment, the researchers say.

The study also showed the collective power of even a relatively small group of cells, Sun added.

“When we hear the rhythms of music, observe the turn signal of the car in front of you, or count the waves on the beach, our brain senses periodicity and predicts when the next event in the sequence will occur,” he said. “But does this function require the full power of the brain? Can a minimal system as simple as a layer of nerve cells sense periodic input? We have shown that this is possible, and that neural cells to do this by forming and organizing a communication network based on signal repetition.’

The findings were published in Proceedings of the National Academy of Sciences.