Mechanical properties of sickle cell membranes

Abstract

The mechanical properties of sickle erythrocyte membranes were evaluated in the ektacytometer. When ghosts from the total red blood cell population were examined, the rigidity of the resealed ghosts and their rate of fragmentation by shear stress (t1/2) were normal. However, fractionation on Stractan density gradients revealed that sickle cells were heterogenous in their membrane mechanical properties. The ghosts from dense cell fractions exhibited both increased rigidity and decreased stability. Presumably, these altered mechanical properties are a reflection of the well-documented biochemical damage found in irreversibly sickle cell membranes. Nevertheless, neither of the alterations in mechanical properties are likely to be significant elements in the hemolysis of sickle cell anemia. Earlier studies of abnormal erythrocytes suggest that increases in membrane rigidity per se do not increase hemolysis, and they are, therefore, unlikely to do so in this case. The stability of membranes from the dense cell fractions was reduced to about two thirds of the control value. Comparison with the results of studies of red blood cell membranes with genetically defective or deficient spectrin suggests that a reduction in t 1/2 of 50% is not associated with significant increases in the rate of hemolysis. Although altered ghost stability and flexibility can be demonstrated in dense sickle cells, these changes in membrane mechanical properties are not likely to be significant factors in the hemolytic process.

Rheological properties of sickle erythrocytes in patients with sickle‐cell anemia: The effect of hydroxyurea, fetal hemoglobin, and α‐thalassemia

“…Sickle RBCs are mechanically fragile, and dense sickle RBCs are particularly susceptible to mechanical damage, probably because of decreased membrane stability. 30 Because patients with SS and α-thalassemia have decreased numbers of dense cells, it is likely that their RBCs are less mechanically fragile. This, in turn, may be a contributing factor to the decreased hemolytic rate observed in these individuals.…”

Sickle Red Cell Microrheology and Sickle Blood Rheology

“…They found that cellular dehydration and the consequent increase in cytoplasmic viscosity are major determinants of the abnormal rheologic behavior of oxygenated sickle cell anemia RBC. Studies on resealed ghosts showed that membrane changes of sickle cell anemia RBC, such as altered material properties, increased extensional rigidity, and decreased membrane stability (53,89), contribute to the abnormal deformability of sickle cell anemia RBC.…”

“…Besides being poorly deformable, oxygenated sickle cell anemia RBC are susceptible to mechanically induced cell fragmentation. In vitro studies have documented increased sensitivity of sickle RBC to mechanical fragmentation following exposure to fluid shear stress (89). The most dense cells are most susceptible to mechanical damage, probably due to weakening of the skeletal protein interactions (spectrin-spectrin or spectin-actin-protein 4.1) as a result of accumulated oxidative damage.…”

“…This finding may explain the better state of hydration of α-thalassemia RBC. Sickle RBC are mechanically fragile and dense sickle RBC are particularly susceptible to mechanical damage probably from decreased membrane stability (89,96). Because subjects with sickle cell anemia and α-thalassemia have reduced numbers of dense cells, it is likely that their RBC are less mechanically fragile.…”

Influence of sickle hemoglobin polymerization and membrane properties on deformability of sickle erythrocytes in the microcirculation

“…In addition to cell suspension studies, viscometry is also useful for determining the rheological properties of Hb S solutions (Briehl, 1981;Chien et al, 1982;Danish et al, 1987;Drasler et al, 1989). Recent experimental studies have shown that the overall rheological properties of sickle erythrocytes are strongly influenced by both cell membrane viscoelasticity (Nash et al, 1984;Evans et al, 1984;Drasler et al, 1989;Messmann et al, 1990;Hebbel, 1991) and interior Hb S gelation (Briehl, 1981;Hofrichter et al, 1981;Gabriel et al, 1981;Noguchi and Schechter, 1985;Hofrichter, 1987, 1990;Danish et al, 1987Danish et al, , 1989Clark, 1989).…”