New insights into regulation of erythrocyte shape

Abstract

Two ideas explain the mechanism of shape regulation: the lipid bilayer coupled theory and the protein network scaffold theory. Recently, several important articles have been published on the former theory. However, many phenomena argue against the theory, including behavior of ghosts and triton shells, various types of manipulation of proteins, and fixation of the shape by the addition of large reagents outside the cell. Moreover, hereditary spherocytosis shows normal, uneven distribution of phospholipids, and hereditary and artificial defects of a membrane protein show spherocytes or elliptocytes. The liquid state of the lipid layer does not seem to support the shape or mechanical characteristics. On the other hand, all of these phenomena argue for the protein network scaffold theory. Characteristics of each protein and interactions among proteins are now being clarified, but this theory and the author's own ideas still lack decisive evidence.

A hypothesis of the disc–sphere transformation of the erythrocytes between glass surfaces and of related observations

“…It differs qualitatively from mechanical models in that the membrane skeleton by its high conformational flexibility is used to generate different shapes, and that Band 3 conformation determines the membrane skeleton conformation. This function of the membrane skeleton is consistent with proposals that it plays a more dominant role than the lipid bilayer asymmetry in determining the erythrocyte shape (Elgsa¨-eter et al, 1986;Nakao, 2002). A consequence of this mechanism is that the membrane skeleton has a negligible or no elasticity and that Band 3 conformation is altered directly or indirectly by mechanical and chemical stresses as they occur in the blood circulation, possibly coupled with the dissociation of spectrin tetramer into dimer observed at modest shearing forces .…”

“…While this premise is reasonable, they are unable at present to explain the reappearance of the spicules at the same sites during the repetitive cycle disc-echinocyte transformation and reversal (Furchgott, 1940;Rand et al, 1965;Bessis and Prenant, 1972;Mukhopadhyay et al, 2002). Finally, there are data in disagreement with the Sheetz and Singer's lipid bilayer couple hypothesis (Isomaa et al, 1987;Wong, 1999;Nakao, 2002). Based on this hypothesis, echinocytogenic amphiphilic compounds, generally anionic, intercalate preferentially into the cationic outer leaflet of the lipid bilayer and increase its area, while stomatocytogenic compounds, generally cationic, intercalate preferentially into the anionic inner leaflet and increase its area.…”

Alkaline hemolysis fragility is dependent on cell shape: Results from a morphology tracker

“…5B). Erythrocyte shape is believed to be governed by a combination of bilayer coupling and the membrane-associated cytoskeleton (23). In the future, measurements of cell morphologic changes in the presence of cytoskeleton-disruptive agents or membrane-coupling alteration compounds can be used to discriminate between the two shape-control mechanisms.…”

Hereditary red cell membrane disorders and laboratory diagnostic testing

“…Connections of the two layers depend on different linker proteins with binding sites, respectively, for the cytoplasmic domains of the integral membrane proteins (band 3 and glycophorin C) embedded in the lipid bilayer and specific regions of spectrin proteins in the cytoskeleton (Figure 1a). Yet the process maintaining the biconcave shape of human red cell remains unclear (4,5). Most often, an erythrocyte membrane defect is suspected when the blood smear of a patient with a nonimmune hemolytic anemia presents with red cells of different sizes and shapes.…”