Uncoupling of the Spectrin-Based Skeleton from the Lipid Bilayer in Sickled Red Cells

Abstract

The distribution of spectrin and band 3 in deoxygenated reversibly sickled cells was visualized by immunofluorescence and immunoelectron microscopy. Antibodies against band 3, the major lipid-associated transmembrane protein, labeled the entire cell body, including the entire length of the long protruding spicule, whereas antibodies against spectrin labeled only the cell body and the base region of the spicules. The results suggest that the formation of long spicules during sickling is associated with a continuous polymerization of hemoglobin S polymers, presumably through gaps in the spectrin-actin meshwork, and a subsequent uncoupling of the lipid bilayer from the submembrane skeleton.

Hydrodynamic narrowing of tubes extruded from cells

“…In other words, integral proteins are torn out and dragged into the tube upon extrusion. Although never observed directly in tethers, such a phenomenon has already been evidenced in RBC vesiculation (25) and in membrane spicules of sickled RBCs (26). The description of the slipping contribution to the dynamics of tether growth is beyond the scope of the present paper.…”

Lipid bilayer and cytoskeletal interactions in a red blood cell

“…For example, it has been hypothesized that the pathogenesis of hereditary spherocytosis is related to the weakened bilayercytoskeletal interaction strength, which leads to reduced spectrin density, and the loss of bilayer membrane resulting in reduced surface area (4). In addition, in sickle cell disease, the detachment of the RBC lipid bilayer from the spectrin network owing to hemoglobin polymerization also causes "budding off" of the bilayer, which in turn results in reduced cell deformability (1). Furthermore, when the RBCs pass through the interendothelial slits in the spleen, they undergo severe deformation.…”

“…Under normal conditions, the cytoskeleton is tightly attached to the lipid bilayer from the cytoplasmic side. However, under certain pathological conditions, e.g., in sickle cell disease, the cytoskeleton may become dissociated from the lipid bilayer (1). Although the biomechanics of the two-component erythrocyte membrane have been studied extensively for decades (2), the mechanical properties of the interactions between the lipid bilayer and the cytoskeleton (such as elastic stiffness, viscous friction, and strength) via the pinning connections of transmembrane proteins are still largely unknown.…”

“…The potential of the RBC membrane including these two different components is written as U = U s + U b + U a+v + U int ; [1] where U s is the spectrin's potential energy from the cytoskeleton, U b is the bending energy from the lipid bilayer, U a+v corresponds to the area and volume conservation constraints from the lipid bilayer, and U int is the potential energy of the interaction between the lipid bilayer and the cytoskeleton. The detailed expressions of U s , U b , and U a+v can be found in SI Text.…”

Identification of a 220 kDa membrane‐associated plant cell protein immunologically related to human β‐spectrin

“…In animal cells, the spectrin-based membrane skeleton (MS) is a topographically distinct cytoskeletal structure which, depending on the cell type, can be physically related to various other intercellular cytoskeletal systems [4,.5]. The MS is known to interact with various cytoplasmic and membrane proteins [6,7]. For example, spectrin, the major component of the MS binds to actin, a process which may be mediated by a minor MS protein now referred to as adducin [S].…”