Fibronectin in Layer-by-Layer Assembled Films Switches Tumor Cells between 2D and 3D Morphology
Kiran Bhadriraju, Jennifer S. Hong, Steven P. Lund, Darwin R. Reyes-Hernandez
Cells in tissues dynamically sense and modulate the adhesive and mechanical properties of their surroundings, according to the functional requirements of normal or diseased tissue. In this study, we show that the migratory and morphological responses of a liver tumor cell line can be engineered in vitro by the combination of a naturally derived ECM protein, fibronectin, and a synthetic polyelectrolyte, polyallylamine hydrochloride. Further, tumor and endothelial cells show dramatic differences in short-term adhesion to a combination of polyallylamine hydrochloride and fibronectin, or fibronectin alone, which allowed us to engineer micropatterned heterotypic co-cultures of the two cell types using a microfluidic manifold. The resulting cell cultures elicit spatially encoded, physiologically-relevant cell responses in both cell types. Our results demonstrate that cell- type specific differences in adhesion response to surfaces can be used to create micropatterned co-cultures of tumor and endothelial cells and suggest that this engineered ECM may be useful for studying tumor-endothelial cell interactions, and for developing in vitro tissue models for cancer drug discovery.