Cell Growth on Patterned Substrates
Development of functional cell-based assay technologies is predominantly carried out with planar two-dimensional (2-D) substrates. Our current understanding of cell-substrate interaction is based primarily on in vitro studies of focal and fibrillar (cell surface structures that mediate cell interaction with extracellular matrix) adhesion and our knowledge about the roles of these structures in cell adhesion, migration, signaling and cytoskeletal function is derived primarily from studies on planar 2-D tissue culture substrates. However, in vivo three-dimensional (3-D)-matrix adhesion differs from focal or fibrillar adhesion, which may explain differences in biological activities observed between 2-D and 3-D cell preparations. It has been hypothesized that relative to 3-D, 2-D culture systems are inaccurate representations of the in vivo environment. In addition, providing an appropriate environment to culture cells in 3-D for accelerated drug discovery application can be challenging. The objective of this work is to develop functional native cell-based technologies for accelerated drug discovery with emphasis on voltage-gated ion channels targets. A preliminary study using differentiated human neuroblastoma cells has revealed differences in cellular responses when cultured either in two-dimensional (2D planer substrata or in three-dimensional (3D) hydrogels, supporting the speculation that cellular function observed in 2D is an exaggeration of 3D and, probably, in vivo function. We intends to develop and characterize simple micro and/or nano fabricated 3D substrates that can easily be implemented in drug screening application.
