The development of a physiologically relevant model system to mimic liver functionality is important to improve understanding of how xenobiotic substances are processed. Previous work has suggested that in order to maintain hepatic functionality within a cell culture, a three dimensional framework with structure similar to the acinus is required. In this proposal, the factors controlling the morphogenis of a three dimensional coculture of hepatocytes and endothelial cells will be explored. Initial studies will focus on the ability to determine markers for both hepatocytes and endothelial cells that do not effect the long term viability of the cells. Once appropriate markers have been determined, modification of the surface chemistry to influence the adhesive properties of the cell culture substrate will be used to control the morphogenetic behavior in the hepatocyte/endothelial cell system. A combination of two-photon fluorescence microscopy and enzyme-linked immunosorbent assay (ELISA) will be used to assess the maintenance liver like functionality within the coculture..
