Dextran (dx) in excess of 40,000 MW can induce weak cell aggregation of native human erythrocytes (RBC) and formaldehyde-fixed RBC (F-RBC) by macromolecular bridging. Cellular aggregation is measured both microscopically and by a rheological method in which the relative viscosity ratio,
estimated at sufficiently low shear rates gives an index of the degree of cellular aggregation. The observed aggregation increases to a maximum at a characteristic dx concentration and then diminishes at higher concentrations until it is absent above a characteristic concentration. Elevation of bulk dextran concentration through this range gives proportional increases in adsorbed polymer and is accompanied by increases in the electrophoretically measured zeta potential of the cells. The correlation of the zeta potentials at disaggregation and the low shear behavior of RBC in the presence of dx support the notion that intercellular electrostatic interactions are an important opposing force to polymer bridging and that weak aggregation could be detected by low shear viscometry. To establish the role of cell deformation in the rheological estimation of aggregation, the degrees of aggregation, zeta potentials, and flow behaviors at low shear were compared for deformable RBC and nondeformable F-RBC in media of differing ionic strengths and dextran T-70 concentrations. In contrast to RBC, F-RBC aggregated weakly in the absence of dx at ionic strengths > 0.03 M and higher dx concentrations were required to disaggregate the cells. At high dx concentrations the zeta potentials associated with disaggregation of F-RBC at different ionic strengths were approximately constant but were consistently higher than for RBC. The rheological estimation of aggregation provided a satisfactory index of the extent of cell–cell cohesion for RBC, but it gave no indication of very weak aggregation of F-RBC under the measurement conditions employed.