University of Innsbruck puts cancer under pressure

13 Aug 2025

Fluorescence technique reveals response of cancer cells when physically squeezed.

Researchers from Barcelona's Centre for Genomic Regulation (CRG) and the University of Innsbruck have studied the response of cancer cells to being physically squeezed, behavior that could have implications for therapy or treatment.

As discussed in Nature Communications, the team used fluorescence microscopy to reveal the way that the cells mount an instant energy-rich response as a defensive mechanism.

The team now theorizes that this reaction from the cells is intended to repair DNA damage and survive the crowded environments of the human body.

A range of fluorescence-based techniques have been employed to study the chemical behavior of malignant calls, and as a way to determine the critical margins of a tumor before surgical removal.

The mechanical responses of tumors have also been the subject of research, with optical assessments of cell elasticity and porosity offering a potential route to understanding the way that tumors grow and assist development of anticancer treatments. A recent project at Rice University took a more direct approach and studied how to vibrate cancer cells to destruction.

The Innsbruck and CRG team used two commercial Leica confocal microscope platforms to assess what happened when HeLa cells were subjected to two different kinds of transient compressive stress: one in which the cells were static and compressed to a size of 3 microns with micro-pistons, and another exerting dynamic pressure and constraining cells to varying heights.

"Given the complexity of in vivo mechanical stress dynamics, we focused on a defined, experimentally tractable aspect: how acute mechanical deformation alters nucleus-organelle organization and triggers adaptive metabolic responses," noted the project in its paper.

Blocking tumor growth

Observations showed that within seconds of the cells being squeezed, mitrochondria race to the surface of the cell nucleus and pump in extra ATP, the cell's molecular energy source.

The mitochondria form a halo so tight that the nucleus dimples inward, and the team termed the surface scaffold structures NAMs, for nucleus-associated mitochondria.

Fluorescence microscopy let the team dig deeper into the sequence of events, after it tagged the cells with a specific chromophore activated when ATP enters the nucleus. The fluorescence signal soared by around 60 percent within three seconds of the cells being squeezed, according to the project.

"It's a clear sign the cells are adapting to the strain and rewiring their metabolism," said Fabio Pezzano from the CRG.

The findings could be significant for cancer therapy, since the NAM halos appear more often in nuclei at invasive tumor fronts. If metastatic cells depend on NAM-driven ATP surges, then drugs that block the structures could make tumors less invasive without broadly poisoning mitochondria, and sparing healthy tissues.

"Mechanical stress responses are an underexplored vulnerability of cancer cells that can open new therapeutic avenues,” said Verena Ruprecht from Innsbruck and CRG's Quantitative Cell Biology group.