Traversing behavior of tumor cells in three-dimensional platforms with different topography

Three-dimensional polydimethylsiloxane platforms were developed to mimic the extracellular matrix with blood vessels by having scaffolds with micropatterns, porous membrane and trenches. Precisely controlled physical dimensions, layouts, and topography as well as different surface chemical treatments were applied to study their influences on nasopharyngeal carcinoma cell (10-15 μm in diameter) migration in mimicked platforms over 15-hour of time-lapse imaging. By placing the pores at different distance from the edges of the trenches, pores with different trench sidewall exposures and effective sizes were generated. Pores right next to the trench sidewalls showed the highest cell traversing probability, most likely related to the larger surface contact area with cells along the sidewalls. Straight grating oriented perpendicular to trenches below the top layer increased cell traversing probability. Pore shape as well as pore size influenced the cell traversing probability and cells could not traverse through pores that were 6 μm or less in diameter, which is much smaller than the cell size. Trench depth of 15 μm could induce more cells to traverse through the porous membrane, while shallower trenches impeded cell traversing and longer time was needed for cells to traverse because 3 and 6 μm deep trenches were much smaller than cell size which required large cell deformation. Hydrophobic surface coating on the top layer and fibronectin in pores and trenches increased the cell traversing probability and reduced the pore size that cells could traverse from 8 to 6 μm, which indicated that cells could have larger deformation with certain surface coatings.