Microengineering the environment of mammalian cells in culture

Assays based on observations of the biological responses of individual cells to their environment have the potential to make enormous contributions to cell biology and biomedicine. To carry out well-defined experiments using cells, both the environments in which the cells live and the cells themselves must be well defined. Cell-based assays are now plagued by inconsistencies and irreproducibility, and a primary challenge in the development of informative assays is to understand the fundamental bases for these inconsistencies and to limit them. It now seems that multiple factors may contribute to the variability in the response of individual cells to stimuli; some of these factors may be extrinsic to the cells, some intrinsic. New techniques based on microengineering especially using soft lithography to pattern surfaces at the molecular level and to fabricate microfluidic systems-have provided new capabilities to address the extrinsic factors. This review discusses recent advances in materials science that provide well-defined physical environments that can be used to study cells, both individually and in groups, in attached culture. It also reviews the challenges that must be addressed in order to make cell-based assays reproducible.