A new study shows that ion gradients across cell membranes form a network separate from DNA for rapid cellular decisions. Cells are constantly on the move in a dynamic environment, facing ever-changing conditions and challenges. So how do cells quickly adapt to these environmental fluctuations?

A new study from Moffitt Cancer Center has been published iScience, answers this question by challenging our understanding of how cells work. The research team suggests that cells have a previously unknown information processing system that allows them to make rapid decisions independently of their genes.

For decades, scientists viewed DNA as the sole source of cellular information. This DNA blueprint tells cells how to create proteins and carry out basic functions. However, new research led by Dipesh Niraula, PhD, and Robert Gatenby, MD, at Moffitt has identified a non-genomic information system that works in conjunction with DNA that allows cells to gather information from their environment and quickly respond to changes.

Role of ion gradients

Research has focused on the role of ion gradients across the cell membrane. These gradients, maintained by specialized pumps, require large amounts of energy to generate variable transmembrane electrical potentials. The researchers proposed that the gradients represent a vast storehouse of information that allows cells to continuously monitor their environment.

When information is received at a specific point on the cell membrane, it interacts with special gates in ion-specific channels, which then open, allowing these ions to flow along pre-existing gradients, creating a communication channel. Ion flows trigger a series of events adjacent to the cell membrane, allowing the cell to analyze information and respond to it quickly. When ion fluxes are large or prolonged, they can trigger the self-assembly of microtubules and microfilaments for the cytoskeleton.

In general, the cytoskeletal network provides mechanical support to the cell and is responsible for cell shape and movement. But cytoskeletal proteins are also excellent conductors of ions, the Moffitt researchers noted.

This allows the cytoskeleton to serve as a highly dynamic intracellular network for ion-based information transfer from the membrane to intracellular organelles, including mitochondria, endoplasmic reticulum, and nucleus. The researchers suggested that this system, which allows for rapid and local responses to specific signals, could also produce coordinated regional or global responses to larger environmental changes.

Information and results of the research

“Our work reveals the ability of cells to use transmembrane ion gradients as a communication tool that allows them to quickly sense and respond to changes in their environment,” said Niraula, a researcher in the department of machine learning. “This complex network allows cells to make rapid, conscious decisions that are critical to their survival and function.”

The researchers believe that this nongenomic information system is critical for the formation and maintenance of normal multicellular tissue and suggest that well-defined ion flows in neurons are a specific example of this extensive information network. Disruption of this dynamic may also be a critical component of cancer development.

They showed that their model was consistent with various experimental observations and highlighted several testable predictions that emerged from their model; They hope that future experiments will pave the way for them to test their theory and shed light on the complexities of cellular decision-making.

“This study questions the implicit assumption in biology that the genome is the sole source of information and that the nucleus acts as a kind of central processing unit,” said Gatenby, co-director of the Center of Excellence in Evolutionary Therapeutics. “We present an entirely new network of information that is deeply involved in the intercellular signaling that enables cellular organisms to function,” he said at Moffitt.