Body tissues use electricity to expel weak cells

Inside our bodies, countless decisions play out silently at the cellular level. Some cells divide, some die, and others are forced out when they no longer serve their purpose.

A study from King’s College London and the Francis Crick Institute reveals that epithelial cells use electricity to spot weak neighbors and remove them. This breakthrough offers fresh insight into how diseases like cancer and stroke arise when energy balance within cells is disturbed.

Cells renew constantly

Epithelial cells form the barrier that lines organs, renewing rapidly to stay protective. Their balance depends on extrusion, the process of ejecting damaged or excess cells. This keeps tissues tightly packed and efficient.

If extrusion falters, cell numbers become chaotic, creating openings for disease. Without this constant regulation, unhealthy cells may linger, disrupt organ integrity, and interfere with critical signaling pathways.

Over time, these disturbances can weaken the protective barrier, encourage unchecked growth, and increase vulnerability to conditions such as cancer, chronic inflammation, or infections that compromise overall tissue health and resilience.

Electricity targets weak cells

Earlier work showed that overcrowding forces some cells to be squeezed out mechanically. The latest discovery goes further. It shows that extrusion is not random but targets energy-poor cells. Crowding pushes sodium into cells through specialized ion channels, altering their electrical signals.

Healthy cells restore balance, but weak ones cannot, triggering shrinkage and eventual extrusion. This reveals a precise surveillance system where tissues actively monitor cellular energy, ensuring only the strongest cells remain.

Such control preserves organ stability, while defects in this mechanism may promote disease progression and unchecked cellular growth.

Cells sense crowding with electricity

The researchers noticed a striking prelude to extrusion: cells briefly shrank before being expelled. This stage, termed homeostatic early shrinkage, reflects water leaving the cell.

Roughly 70 percent of extruding cells undergo this shrinkage. It is not caused by contractile forces but by ion channels regulating water movement. Key players include the potassium channels Kv1.1 and Kv1.2, and the chloride channel SWELL1.

The study revealed that an epithelial sodium channel, ENaC, senses crowding. It acts as a tension detector, letting sodium rush in when cells press against one another.

If a cell has enough ATP, it pumps sodium back out and stabilizes. If not, depolarization occurs, potassium and chloride exit, water follows, and the cell shrinks, crossing the threshold that triggers extrusion.

Low energy as a trigger

Time-lapse experiments revealed that cells destined for extrusion show falling ATP levels before they depolarize and shrink. When ATP levels were artificially lowered, extrusion increased.

This shows energy deficiency directly selects cells for removal. In essence, epithelial tissue runs a built-in fitness test: cells unable to maintain their electrical balance are expelled.

“We see this sodium channel acting as a sensor, exposing cells with the least amount of energy and targeting those cells for death,” noted study lead author Dr. Saranne Mitchell.

“This mechanism gives epithelia a constant surveillance system to rapidly detect weak cells and remove them. It’s like an electrical quality-control check, keeping tissues robust and functional.”

Implications for diseases

The study highlights how epithelial tissues are not passive layers but dynamic communities constantly testing their members. By identifying weaker cells early, they can preserve strength and protect organ function.

“By revealing that cells with low energy are targeted for extrusion, our work also adds a new layer into how metabolism can impact many diseases,” said Professor Jody Rosenblatt.

“This new insight could suggest how overconsumption, through eating more and consuming more calories, might override this ‘low energy trigger’ for extrusion and prevent the elimination of defective cells, allowing them to accumulate into cancers.”

“It might also reveal how energy deprivation following a stroke, caused by impacted blood supply, could lead to excess extrusion and organ damage.”

Cells use electricity effectively

This model highlights energy sufficiency as a deciding factor in cell survival. Much like how mitochondria regulate apoptosis, epithelial extrusion uses energy balance as a checkpoint.

The findings also connect to conditions like cystic fibrosis and cancer, where ion channel malfunctions are common. By linking ion flow, energy, and crowding, this study reframes how tissues maintain integrity.

The discovery paints epithelia as more than static barriers. They are dynamic, electrically sensitive tissues constantly probing their members for weakness.

Cells that cannot meet the energy demands are removed for the greater good of the tissue. Even the faintest electrical flicker within these cellular communities can tip the balance between health and disease.

The study is published in the journal Nature.

Image Credit: CC0 Public Domain

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