Investigation of deformability, viscosity, and aggregation of mPEG-modified erythrocytes

Several techniques for the development of a universal blood type are under investigation in order to address the vast shortage of blood required during times of crisis and for those receiving chronic transfusions. Recently, the covalent attachment of methoxypolyethylene glycol (mPEG) has received attention as a means to conceal the major and minor blood antigens that can invoke an immune response. We have utilized a simple method to covalently bind mPEG to the surface of red blood cells and monitored the rheological properties including cellular deformability and suspension viscosity as a function of shear rate and aggregation. In order to simulate the deformability of mPEG-modified erythrocytes through small blood vessels, we have studied the flow of cells through a nickel-mesh membrane with a pore size of 5.8 microns. Using a gravity-based nickel-mesh filtration device, dilute solutions of red blood cells were filtered through a membrane. The pressure drop was monitored with time. We have examined the filterability of whole blood, washed erythrocytes, mPEG-altered erythrocytes, and mixtures of altered erythrocytes with whole blood. Results from this apparatus have suggested that there is a significant decrease in deformability using mPEG-modified erythrocytes compared to unaltered red blood cells at identical concentrations. Increasing the ratio of modified cells to unmodified cells resulted in decreased deformability of the suspension. Viscosity measurements of mPEG-modified red cells have shown a shear-thinning property, while results of aggregation measurements indicate reduced aggregation compared to whole blood.