Mechanobiology studies of bladder tumor cells using laterally squeezing microfluidic flow cytometry

The deformability and uptake capability of cells are critical indicators of their biomechanical properties and functional behaviors, particularly in tumor heterogeneity and cancer research. Here, we introduce a microfluidic flow cytometry platform integrated with a laterally adjustable squeezing structure for the characterization of bladder tumor cells (including 5637 and EJ cell lines) and uroepithelial cells (SV-HUC-1 cell line). The deformability of these cell types under varying channel width conditions was clearly assessed using this platform. The results demonstrated that tumor cells exhibited higher deformability compared to uroepithelial cells, with the EJ cell line exhibiting the greatest difference. Furthermore, the relationship between the malignancy, deformability, and uptake capability of bladder cells was explored through co-cultivation experiments with 2 μm particles. As the malignancy increased, the cells became more deformable and exhibited stronger phagocytic capability with particles. Subsequently, the heterogeneity of tumor cells was investigated by analyzing the deformability of phagocytic and non-phagocytic subpopulations within EJ cells. The developed microfluidic platform offers a promising high-throughput method to assess the biomechanical and phagocytic characteristics of cells, providing valuable insights into tumor cell biology, and potentially improving clinical status of urinary cytology examinations for bladder cancer.