Abstract
A dense aggregate of cells was retained in a reactor by a supported porous membrane. A continuous flow of nutrient medium was maintained through the cell aggregate and membrane. The hydraulic resistance of the cell aggregate was monitored throughout experiments with either growing or chemically cross-linked cells, under conditions of varying flow rates. Digital image analysis was used to characterize the sizes, separations, and orientations of several thousand individual cells in electron micrographs of chemically cross-linked cell aggregates. Two nonlinear phenomena were observed. First, the hydraulic resistance varied in direct relation to and reversibly with flow rate. Second, in constant flow-rate experiments the hydraulic resistance increased with time at a faster rate than could be attributed to cell growth. Both of these phenomena were dependent upon and could be explained by the ability of cells to move with respect to one another, under the influences of Brownian motion and of convection. Such relative motion could allow changes in net alignment of cells in the direction of flow and in the volume fraction of cells in the aggregate. This explanation is consistent with image analysis data. The observed sensitivity of hydraulic resistance to flow rate was inconsistent with a model that assumed elastic deformation of individual cells, and no evidence of cell deformation was found in electron micrographs.
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