Three Rheologic States of Erythrocytes Depending Upon Increasing Shear Rate. Each state, tumbling (flipping), rolling (spinning), and tank-treading/swinging shows one erythrocyte with sequential changes in flow from left to right. In each rheologic state, the erythrocyte has a black dot representing an adherent microbead, as used experimentally to mark a location on the red cell membrane. At low shear rates on the left, the erythrocyte tumbles (flips) while maintaining membrane solidity so that the microbead remains in the same location relative to the rest of the cell. As the shear rate is increased (left green arrow), the orientation of the erythrocyte in the shear plane allows a wheel-like rolling, while the microbead remains in the same location because the membrane remains relatively solid. With further increases in shear rate, the rolling erythrocyte reorients itself by 90 degrees, so that it is spinning while maintaining membrane solidity. With even further increases in shear rate (right green arrow), the erythrocyte membrane fluidity reaches the point at which the membrane rotates around the cytoplasm (tank-treads), and the microbead moves relative to its former location on the erythrocyte. The tank-treading erythrocyte maintains its basic biconcave shape, but it has slight fluctuations in its orientation so that it “swings” relative to the shear plane.
Three Rheologic States of Erythrocytes Depending Upon Increasing Shear Rate. Each state, tumbling (flipping), rolling (spinning), and tank-treading/swinging shows one erythrocyte with sequential changes in flow from left to right. In each rheologic state, the erythrocyte has a black dot representing an adherent microbead, as used experimentally to mark a location on the red cell membrane. At low shear rates on the left, the erythrocyte tumbles (flips) while maintaining membrane solidity so that the microbead remains in the same location relative to the rest of the cell. As the shear rate is increased (left green arrow), the orientation of the erythrocyte in the shear plane allows a wheel-like rolling, while the microbead remains in the same location because the membrane remains relatively solid. With further increases in shear rate, the rolling erythrocyte reorients itself by 90 degrees, so that it is spinning while maintaining membrane solidity. With even further increases in shear rate (right green arrow), the erythrocyte membrane fluidity reaches the point at which the membrane rotates around the cytoplasm (tank-treads), and the microbead moves relative to its former location on the erythrocyte. The tank-treading erythrocyte maintains its basic biconcave shape, but it has slight fluctuations in its orientation so that it “swings” relative to the shear plane.
The main function of erythrocytes, the transporting of gasses (oxygen, carbon dioxide, and nitric oxide) involved in tissue respiration, occurs in small vessels. Shear forces on erythrocytes vary as blood flows from small arterioles through capillaries into venous sinuses. Under conditions of low and moderate shear force experienced in small vessels, the rheologic properties of human erythrocytes are largely determined by specific changes in their shape and motion. Two basic motions of erythrocytes (Figure) have previously been described as tumbling or flipping when exposed to low shear rates, and tank-treading when the shear rate and/or the viscosity of the suspending medium are increased. The membrane of a tank-treading erythrocyte has fluidity and elasticity that allows its rotation around the hemoglobin-filled cytoplasm, while the biconcave shape is maintained at moderate shear rates, and a more ellipsoid shape is assumed with higher shear rates.1 When the shear force is removed, the formerly tank-treading erythrocyte membrane reorients itself to assume the same position relative to the rim and biconcave dimples that it had prior to the initiation of tank-treading (i.e., erythrocytes have shape memory).1
In their videomicroscopy study, Dupire et al. demonstrated that at low and moderate shear rates, erythrocytes maintain their biconcave shapes with only slight long-axis distortion. With low shear rates, an erythrocyte tumbles or flips. As the shear rate is increased, the tumbling erythrocyte can undergo a transition in its orientation so that it rolls like a wheel. This tumbling-to-rolling transition requires a limited amount of membrane elasticity, but after achieving the rolling orientation, the energy expended in cell shape maintenance is minimized compared with that expended in preserving cell shape during tumbling or that expended in the membrane rotation of tank-treading. At progressively higher shear rates, the rolling erythrocytes undergo a 90-degree orientation change to a Frisbee-like spinning motion that precedes a transition to tank-treading with fluctuations of the angle of orientation in the shear plane, a process termed swinging.2
Dupire and colleagues demonstrated specific transition states as an erythrocyte goes from rolling/spinning to tank-treading and also when it makes the opposite transition from tank-treading directly to tumbling. In the former transition, focal areas of the membrane appear to remain solid as the rest of the membrane has acquired the fluid movement of tank-treading. In the transition from tank-treading to tumbling caused by decreasing shear rate, the erythrocytes have short periods in which tank-treading is interrupted by one or two flips of the erythrocyte before there is complete loss of membrane fluidity and a return to a tumbling motion.
In Brief
The fascinating studies of Dupire et al. demonstrate that transitions in cell shape and motion in response to changes in shear rate may help erythrocytes adapt to the vicissitudes of transit through the various components of the microvasculature, but future experiments will be needed to verify the roles of these rheologic changes in vivo. Characterization of the rheologic properties of normal erythrocytes enhances our understanding of the pathophysiology of diseases that involve abnormalities of the erythrocyte membrane, serum viscosities, and microvessels, including sickle cell anemia, malaria, polycythemia, macroglobulinemia, vasculitis, and diabetes.;
