Morphological Control of Cells on 3-Dimensional Multi-Layer Nanotopographic Structures

The extracellular matrix (ECM) environment is known to play an important role in the process of various cell regulatory mechanisms. We have investigated the ability of 3-dimensional ECM geometries to induce morphological changes in cells. Bi-layer polymeric structures with submicron scale stripe patterns were fabricated using a two-step nano-imprinting technique, and the orientation angle (theta(alpha)) of the upper layer was controlled by changing its alignment with respect to the orientation of the bottom layer. When cells were grown on the mono-layer stripe structure with a single orientation, they elongated along the direction of the stripe pattern. On bi-layer polymer structures, the cell morphologies gradually changed and became rounded, with an increase of theta(alpha) up to 90 degrees, but the polarities of these cells were still aligned along the orientation of the upper layer. As a result, we show that the polarity and the roundness of cells can be independently regulated by adjusting the orientation of 3-dimensional hierarchical ECM topography.