Cell death often spreads in chains like a fire, but why don't human tissues burn up and be destroyed all the way? A team led by Chen Shenghong, associate researcher at the Institute of Molecular Biology, Academia Sinica, discovered that cells will form a natural "firewall" to prevent the spread of death through their own arrangement, just like a building with fire protection zones to prevent the spread of fire. The study also found that the density and direction of cell arrangement can determine the propagation path of the death wave. The research results were published yesterday in the top international journal "Cell".
Cell death is not always a bad thing. For example, when a tadpole develops into a frog, its tail gradually disappears, which involves the regulation of cell death. But if death gets out of control, massive tissue damage can occur. Chen Shenghong's team discovered in the journal "Nature" in 2024 that "ferroptosis" can form a "trigger wave" similar to a wave or domino effect, which continues to spread from a few cells to the surroundings, causing large-scale cell death.
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Ferroptosis is a type of cell death triggered by lipid oxidation, which is different from general apoptosis. Since the death wave can continue to spread, how can human tissue stop it? It has become an important issue for the team to continue to study.
Chen Shenghong said that researchers observed cell death waves through microscopes for a long time. The first authors, postdoctoral fellows Zheng Renhao and Hannah Katrina C.Co of the Institute of Merism, discovered that the density and direction of cell arrangement will affect the propagation of death waves. The team further confirmed that the spatial structure of the organization itself is an important factor in determining where the death wave starts, in which direction it propagates, and when it stops.
Chen Shenghong used a map metaphor. The arrangement of cells is like a map, which can not only guide the path of the death wave, but also build a defense line to prevent the spread of death. Areas with lower cell density and irregular arrangement are more likely to undergo ferroptosis; areas with higher cell density and neat arrangement have stronger resistance and even form natural boundaries.
Studies have also found that cell arrangement changes internal lipid distribution. When cells are elongated and aligned in the same direction, easily oxidized lipids will be concentrated at both ends of the cell, causing the death wave to advance along the direction of alignment rather than spreading evenly around.
As for future medical applications, Chen Shenghong pointed out that the research team hopes to further use cell arrangement to understand the propagation of death waves in human tissues and cancer. For example, how cell death spreads after heart tissue is damaged, and whether cell arrangement affects the death wave during cancer metastasis, are worthy of in-depth study.
The current research mainly uses cultured human epithelial cells as a model. In the future, it will be further verified in animal tissues and humans. It will also explore related mechanisms such as embryonic development, organ damage, degenerative diseases and cancer. Chen Shenghong emphasized that it is still basic research and is still some way away from clinical application, but it has provided a new research direction for understanding and regulating large-scale cell death.
