Description
Collective cell behavior generates a multitude of cellular patterns that exhibits specialized cell alignments, densities and macroscopic structures through cell self-organization. The formation of these cellular patterns serves as a foundation for morphogenesis and development. Despite the ubiquity of cellular patterns in tissues, how it may impact the homeostasis of the entire cell population in the face of stress remain unexplored. Here, we showed that the emergent cellular patterns can prime cells for differential sensitivity to ferroptosis, an iron and lipid peroxidation-dependent form of cell death. Ferroptosis induced large-scale cell death has been shown to propagate without spatial limitation as trigger waves, threatening the viability of the whole cell population. However, in the presence of self-organized cellular patterns, cell death propagation is oriented in direction and speed by the spatial arrangements of cells, resulting in distinct spatial distributions of dead and surviving cells. The wave initiates in areas of cellular misalignment and lower cell density, particularly at sites of specific cellular patterns known as topological defects. Once initiated, the wave travels rapidly along aligned cells, but decelerates when encountering cells oriented against its path or when passing through high density regions. We further discovered this phenomenon is attributed to the polarized distribution of oxidizable lipids in the membrane of individual cells. Our findings show self-organized cellular patterns in a cell population direct propagation of large-scale ferroptotic cell death, featuring how collective cellular behavior in tissues and organs influences vulnerability to ferroptosis.
