Decoding stress-induced adaptation of cancer cells in spatial confinement by integrating live-cell imaging and mathematical modeling

In cisplatin-sensitive and -tolerant lung cancer spheroids in microfluidics, spatial organization and dynamic microenvironment remodeling govern population fitness, with tolerant cells showing persister-like cooperation.

• Why it matters: Tumor microenvironments impose confinement, yet stress adaptation in such spatially restricted settings is less understood than in 2D cultures and related evolutionary game theory frameworks.
• What they did: The study grew monotypic or heterotypic spheroids of cisplatin-sensitive and -tolerant lung cancer cells in a microfluidics system, tracked them live, and fit a modified Cellular Potts model to estimate interaction and competition parameters.
• The result: Sensitive and tolerant populations used different cooperative/competitive strategies under changing conditions, and tolerant cells appeared persister-like and cooperative with sensitive cells, enabling chemotherapy evasion.

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