Alteration of the mechanical properties of sickle cells by repetitive deoxygenation: role of calcium and the effects of calcium blockers

Nash, Gerard B.; Boghossian, S.; Parmar, J.; Ja, Dormandy; Bevan, David

doi:10.1111/j.1365-2141.1989.tb07692.x

Cited by 27 publications

(9 citation statements)

References 15 publications

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“…We previously showed that when less dense sickle cells were subjected to 15 hr of cyclical deoxygenationreoxygenation in the presence of calcium, they lost potassium and water via the Gardos channel and a proportion became ISC; 15-hr incubation without deoxygenation did not affect these parameters [26]. Here, cyclically deoxygenated cells showed significantly higher adhesion than control cells incubated at 37°C but kept fully oxgenated (Table 111).…”

Section: Effect Of In Vitro Incubation and Formation Of Dense Cellsmentioning

confidence: 86%

Effects of density and of dehydration of sickle cells on their adhesion to cultured endothelial cells

1996

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Abnormal adhesion of sickle cells to vascular endothelium may be a factor in the initiation of painful vaso-occlusive crisis. The sickle cell population contains an unusually large number of less dense reticulocytes that are known to be more adhesive than mature red cells, but there is contradictory evidence regarding the adhesiveness of dense sickle cells. We used a flow-based assay of adhesion to cultured human umbilical vein endothelial cells to test the properties of density fractions of sickle cells, prepared either by density gradient or by centrifugation of packed cells. We also examined the effects of incubating sickle cells with or without cyclical deoxygenation on their adhesion. After fractionation on a Percoll-lsopaque gradient, the less dense 10% (reticulocyte-rich) cells and the most dense 10% cells adhered in greater number than the remainder (by about twofold). However, after centrifugation of packed cells, the less dense 10% were again more adhesive than the "middle" cells, but the most dense were not. Exposing sickle cells to constituents of the gradient had no consistent effect on adhesion, while centrifugal packing induced a degree of hemolysis, and tended to reduce adhesiveness of the dense fraction previously obtained from a gradient. Incubation in air at 37°C for 15 hr reduced the number of reticulocytes and the adhesiveness of less dense sickle cells compared to those held at 4°C. On the other hand, incubation at 37°C for 15 hr with cyclical deoxygenation caused formation of dense cells and increased adhesiveness compared to incubation without cyclical deoxygenation. We conclude that young, less dense sickle cells are unusually adhesive, but that this adhesiveness is reduced during maturation. However, repeated sickling in vivo causes formation of an abnormally dense subpopulation of cells which either redevelop an increased tendency to adhere to endothelial cells or preserve their initial adhesiveness. Both adhesive cell populations may be implicated in promoting vascular obstruction.

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Section: Effect Of In Vitro Incubation and Formation Of Dense Cellsmentioning

confidence: 86%

Effects of density and of dehydration of sickle cells on their adhesion to cultured endothelial cells

1996

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“…At the onset of crisis, identification of the prodromal phase allowed the detection of a sub-population of poorly deformable dense cells that would not have been detected had the study been limited to the later phase of established crisis. Formation of dense, poorly deformable sickle cells may occur continuously in vivo, because of repeated cycles of deoxygenation and reoxygenation (Nash et al, 1989), with accelerated removal during vaso-occlusive events. The implication of the present study is that this subpopulation had increased sufficiently to become an initiating factor in vaso-occlusive crisis.…”

Section: Discussionmentioning

confidence: 99%

Rheological changes in the prodromal and established phases of sickle cell vaso‐occlusive crisis

et al. 1992

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A rheological study has been made in 20 patients with sickle cell anaemia in the steady state and in the prodromal and established phases of 12 vaso-occlusive crises. Rheology of sickle cells was studied by discontinuous density gradient fractionation and by filtration through pores of 5 microns diameter. The prodromal phase of crisis (day 1), when compared with mean steady state values, was associated with the development of a sub-population of poorly deformable dense cells. This sub-population appeared 1 or more days before the acute-phase rise in C-reactive protein, orosomucoid, fibrinogen, plasma viscosity and leucocytes, and before the rise in serum lactate dehydrogenase. As crisis evolved, the sub-population decreased to steady-state values, or below, by days 6-7. Identification of the prodromal phase of sickle cell crisis has allowed the detection of rheological changes of potential aetiological significance.

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“…Specifically, the goal was to obtain leaflet compressibility from area fluctuations in the spirit of the above-described theory (Eqs. [2][3][4][5].…”

Section: Methodsmentioning

confidence: 99%

“…A cell's ability to take on distinct shapes is directly dependent on the flexibility of its bounding plasma membrane (PM), and thus maintaining a certain level of flexibility of the PM is essential to both cell and human physiology. A prominent example of the consequences of deficits in PM flexibility is sickle cell anemia, a disease characterized by a drastic change in the shape and stiffness of red blood cells that leads to their accumulation on vessel walls and blockage of blood flow [1][2][3][4][5][6].…”

Section: Introductionmentioning

confidence: 99%

A new computational method for membrane compressibility: Bilayer mechanical thickness revisited

Doktorova

Levine

Khelashvili

et al. 2018

Preprint

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Because lipid bilayers can bend and stretch in ways similar to thin elastic sheets, physical models of bilayer deformation have utilized mechanical constants such as the moduli for bending rigidity ( " ) and area compressibility ( $ ). However, the use of these models to quantify the energetics of membrane deformation associated with protein-membrane interactions and the membrane response to stress is often hampered by the shortage of experimental data suitable for the estimation of the mechanical constants of various lipid mixtures. While computational tools such as Molecular Dynamics (MD) simulations can provide alternative means to estimate $ values, current approaches suffer significant technical limitations. Here, we present a novel computational framework that allows for a direct estimation of $ values for individual bilayer leaflets. The theory is based on the concept of elasticity and derives $ from real-space analysis of local thickness fluctuations sampled in MD simulations. We explore and validate the model on a large set of single and multicomponent bilayers of different lipid composition and sizes, simulated at different temperatures. The calculated bilayer compressibility moduli agree with values estimated previously from experiments and those obtained from a standard computational method based on a series of constrained tension simulations. We further validate our framework in a comparison with an existing polymer brush model (PBM) and confirm the PBM's predicted linear relationship with proportionality coefficient of 24 using elastic parameters calculated from the simulation trajectories. The robustness of the results that emerge from the new method allows us to revisit the origins of the bilayer mechanical (compressible) thickness and in particular, its dependence on acyl chain unsaturation and the presence of cholesterol.All rights reserved. No reuse allowed without permission.was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.

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Alteration of the mechanical properties of sickle cells by repetitive deoxygenation: role of calcium and the effects of calcium blockers

Cited by 27 publications

References 15 publications

Effects of density and of dehydration of sickle cells on their adhesion to cultured endothelial cells

Effects of density and of dehydration of sickle cells on their adhesion to cultured endothelial cells

Rheological changes in the prodromal and established phases of sickle cell vaso‐occlusive crisis

A new computational method for membrane compressibility: Bilayer mechanical thickness revisited

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