Abstract
Migration of cancer cell is a cyclic process, which involves dynamic interaction between extracellular biointerface and cellular responds. In tumors, collagen as extracellular matrix reorganizes biointerface from curl and isotropic fibers to straightened and anisotropic fibers during tumorigenesis, yet how cell migration respond to topography of biointerface is unknown. In this research, we introduced a facile fabrication method on nanofibers of varying topography, which was mimicking the alignment of extracellular nanofibers, to examine the change of cytoskeleton during cell migration. We took advantage of breast carcinoma cell line (MDA-MB-231) for time-lapse imaging analysis. We found that biointerface anisotropy modulated morphology of cell and mediated the pattern of migration. Morphologically, cells on anisotropic nanofiber showed extending spindle shape. The trajectories of migration templated the topographic pattern on biointerface. Besides, aligned nanofiber induced caterpillar-like model of migration through protrusion - retraction cycle, which was indicated by periodical variation of aspect ratio and velocity of cells. The biointerface anisotropy triggered vimentin filaments and microtubule networks preferentially oriented along the alignment of nanofibers. And the velocity of cell mobility by vimentin, β-catenin or CDC42 knockdown was significantly enhanced on aligned nanofibers. Thus, we implied that biointerface anisotropy modulated migration of breast cancer cell and it associated with reorganization of cytoskeleton filaments.
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