Responses of Cellular Adhesion Strength and Stiffness to Fluid Shear Stress during Tumor Cell Rolling Motion

Biochemical and physical factors affect the rolling of tumor cells across the blood vessel. The biochemical factors have been well studied, while the influence of physical factors such as fluid shear stress (FSS) remains poorly understood. Here, human glioma cells (U87 cells) in a straight microfluidic channel were exposed to FSS (0.12, 1.2, and 1.8 dyn/cm²); and their locomotion behaviors from crawling-to-rolling and changes in cellular morphology (concave, elongated, less elongated, and round) were observed. The adhesion strength and stiffness of the cells of different morphologies were analyzed using a live single-cell extractor and atomic force microscopy, respectively. In general, the FSS stimulated cells showed stronger adhesion strength than the cells not exposed to FSS. The cell not exposed to FSS always exhibited greater nuclear stiffness than cortex stiffness, while after FSS treatment the cortex hardened and nucleus softened, where the round-shaped cell had a cortex that was more rigid than its nucleus. These results indicated that FSS influenced the biomechanics of circulating tumor cells, and elucidation of the mechanical responses to FSS might provide a deeper insight for cancer metastasis.