A study led by Verena Ruprecht and Sara Sedlchek, published in Nature Communications, has shown that cancer cells respond instantly to physical compression with a powerful energy boost. This is the first documented protective mechanism that helps cells repair DNA damage and survive in crowded environments.
Researchers from the University of Innsbruck and the Centre for Genomic Regulation (CRG) in Barcelona used a microscope capable of compressing living cells to just three micrometers thick — about one-thirtieth the diameter of a human hair. Within seconds, mitochondria in HeLa cells moved toward the nucleus and released additional ATP, the main cellular energy source.
The team named these structures “nuclear-associated mitochondria” (NAM). In compressed cells, NAM formed a dense halo around the nucleus, increasing nuclear ATP levels by 60% in just three seconds. This energy surge enabled cells to repair DNA damage caused by mechanical stress, whereas uncompressed cells failed to divide properly.
To validate the findings, researchers examined breast tumor biopsies from 17 patients. NAM halos were observed in 5.4% of nuclei at invasive fronts of tumors — three times higher than in dense tumor cores.
Further investigation revealed that actin filaments and the endoplasmic reticulum form a scaffold that holds NAM around the nucleus. Disrupting actin prevented NAM formation and reduced ATP delivery.
Scientists suggest this mechanism could offer new therapeutic opportunities: targeting NAM may reduce tumor invasiveness without harming healthy tissue. They also believe similar responses to mechanical stress may occur in other cell types, including immune cells, neurons, and embryonic cells.
Dr. Sara Sedlchek commented, “This represents a completely new level of cellular regulation, reshaping our understanding of how cells cope with intense physical stress.”
