Cell Adhesion in Animal Cell Culture: Physiological and Fluid-Mechanical Implications

We have reviewed the general forces through which cells interact with substrata in their first nonspecific contact. The complex, fast-emerging biology of specific cell adhesion and the structure of the extracellular matrix were reviewed in substantial detail, and the most updated conceptual model of biological cell adhesion was assembled from past efforts and new literature data. The chemistries of the various possible substrata for cell adhesion have been reviewed extensively in the past, and here only a brief summary was presented, with particular emphasis on the materials for traditional and porous microcarriers. The fascinating molecular and cellular implications of cell adhesion were reviewed in detail to establish that cell adhesion and the extracellular matrix provide more than structural support for the cells and their assemblies, and that in fact they constitute fundamental regulators of cell function, metabolism, and differentiation. We reviewed the fluid-mechanical mechanisms of cell damage in microcarrier systems and provided experimental evidence for the importance of the cell-adhesion quality in the ability of cells to withstand fluid forces in bioreactors. We provided evidence that the interplay of cell adhesion and fluid forces is likely to produce cell responses more complex than that of simple life and death, and we suggested that such responses are awaiting investigation and exploration for new applications and culturing possibilities. We also reviewed the experimental evidence on the importance of cell adhesion in cell and microcarrier aggregation and discussed the implications of such aggregation on the culturing environment and the operation of bioreactors. Finally, we discussed the possible implications of cell adhesion as it relates to the developing field of tissue engineering, using the example of bone marrow culture, which involves a large variety of cells and constitutes one of the most complex cell culture systems.