Microengineering the Environment of Mammalian Cells in Culture
- PDF / 1,046,947 Bytes
- 8 Pages / 612 x 792 pts (letter) Page_size
- 103 Downloads / 251 Views
Microengineering the Environment of Mammalian Cells in Culture
Christopher S. Chen, Xingyu Jiang, and George M. Whitesides Abstract 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. Keywords: biosensors, cell-based assays, diagnostics, microfabrication, microfluidics, PDMS, poly(dimethylsiloxane), soft lithography.
Introduction Cells are the fundamental living units of organisms: the response of an organism to disease, injury, or therapy is the response of its cells. To be able to model life and predict the response of organisms to therapeutic or pathological stimuli ultimately requires the ability to model the behavior of the cells (individually) and tissues (as collections of cells) to these stimuli. Thus, characterizing the full range of cellular behaviors, mapping these behaviors to normal function and to disease, and reducing these behaviors to molecular processes are three of the primary goals of biomedical research. The study of the molecular aspects of cells, especially understanding the genome and how the information it encodes is converted into proteins, has exploded in the last
194
40 years. Understanding how the phenotype (the actualized cellular characteristics, processes, and behaviors, such as shape, size, growth rate, migratory behavior, and response to stimuli) arises from its genotype (molecular composition) is, however, a much more complex subject and is only just beginning to be explored. Both approaches—the “top-down” study of cells, beginning with phenotypic cellular behaviors, and the “bottom-up” study of nucleic acids, proteins, and networks of reactions—must ultimately combine if we are to fully understand the cell. Even without this full understanding, however, the ability to modulate the phenotype of cells is potentially enormously useful. These behaviors are the result of the
operation of all the proc
Data Loading...
