Rheological Comparison of Hemoglobin Solutions and Erythrocyte Suspensions

Cokelet, Giles R.; Meiselman, Herbert J.

doi:10.1126/science.162.3850.275

Cited by 169 publications

(101 citation statements)

References 7 publications

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“…8). The data agree with those obtained by others on Hb AA (20,(23)(24)(25) as well as on Hb SA hemolysates (25). An increase in hemoglobin concentration up to the normal MCHC (32 g/100 ml) caused a relatively slight rise in viscosity, but further elevations in hemoglobin concentration resulted in a sharp increase in viscosity (Fig.…”

Section: Resultssupporting

confidence: 82%

“…Therefore deformability of erythrocytes, a property which results in a lowering of viscosity at high shear rates (28), de- pends on the internal viscosity 2 of the hemoglobin-rich solution as well as on the flexibility of the membrane' (20,29,31,32 (Table II) and, according to the data shown in Fig. 8, presumably possess similar internal viscosities.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Abnormal rheology of oxygenated blood in sickle cell anemia

Chien¹,

Usami²,

Bertles³

1970

J. Clin. Invest.

309

151

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A B S T R A C T The viscosity of oxygenated blood from patients with sickle cell anemia (Hb SS disease) was found to be abnormally increased, a property which contrasts with the well recognized viscous aberration produced by deoxygenation of Hb SS blood. Experiments designed to explain this finding led to considerations of deformation and aggregation, primary determinants of the rheologic behavior of erythrocytes as they traverse the microcirculation. Deformability of erythrocytes is in turn dependent upon internal viscosity (i.e. the state and concentration of hemoglobin in solution) and membrane flexibility. Definition of the contribution made by each of these properties to the abnormal viscosity of oxygenated Hb SS blood was made possible by analysis of viscosity measurements, made over a wide range of shear rates and cell concentrations, on Hb SS erythrocytes and normal erythrocytes suspended in Ringer's solution (where aggregation does not occur) and in plasma. Similar

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Section: Resultssupporting

confidence: 82%

Section: Resultsmentioning

confidence: 99%

Abnormal rheology of oxygenated blood in sickle cell anemia

Chien¹,

Usami²,

Bertles³

1970

J. Clin. Invest.

309

151

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“…As presented in Table 1, we discover surprisingly high values for the effective viscosity (Ϸ100 ϫ 10 Ϫ3 Pa s) compared with literature values for RBC viscosity, which was reported to be approximately RBC Ϸ10 ϫ 10 Ϫ3 Pa s (18). Such an increase of the effective viscosity at the membrane was predicted to be a confinement effect caused by close association of the spectrin to the membrane, providing a steric obstacle for the fluid flow (19).…”

Section: Discussionsupporting

confidence: 51%

ATP-dependent mechanics of red blood cells

Betz

Lenz

Joanny

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

298

371

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Red blood cells are amazingly deformable structures able to recover their initial shape even after large deformations as when passing through tight blood capillaries. The reason for this exceptional property is found in the composition of the membrane and the membrane-cytoskeleton interaction. We investigate the mechanics and the dynamics of RBCs by a unique noninvasive technique, using weak optical tweezers to measure membrane fluctuation amplitudes with s temporal and sub nm spatial resolution. This enhanced edge detection method allows to span over >4 orders of magnitude in frequency. Hence, we can simultaneously measure red blood cell membrane mechanical properties such as bending modulus ‫؍‬ 2.8 ؎ 0.3 ؋ 10 ؊19 J ‫؍‬ 67.6 ؎ 7.2 kBT, tension ‫؍‬ 6.5 ؎ 2.1 ؋ 10 ؊7 N/m, and an effective viscosity eff ‫؍‬ 81 ؎ 3.7 ؋ 10 ؊3 Pa s that suggests unknown dissipative processes. We furthermore show that cell mechanics highly depends on the membrane-spectrin interaction mediated by the phosphorylation of the interconnection protein 4.1R. Inhibition and activation of this phosphorylation significantly affects tension and effective viscosity. Our results show that on short time scales (slower than 100 ms) the membrane fluctuates as in thermodynamic equilibrium. At time scales longer than 100 ms, the equilibrium description breaks down and fluctuation amplitudes are higher by 40% than predicted by the membrane equilibrium theory. Possible explanations for this discrepancy are influences of the spectrin that is not included in the membrane theory or nonequilibrium fluctuations that can be accounted for by defining a nonthermal effective energy of up to Eeff ‫؍‬ 1.4 ؎ 0.1 kBT, that corresponds to an actively increased effective temperature.erythrocyte ͉ membrane fluctuations ͉ nonequilibrium ͉ optical tweezer ͉ spectrin T he extraordinary deformability of RBCs is vital for their proper function, as it enables the cells to be elongated by more than twice their size when passing through m-sized capillaries. The elastic properties of RBCs are dominated by the interaction between the cell membrane and the underlying cytoskeleton, mainly consisting of spectrin, a long heterodimer that aligns tail to tail forming a 200-nm-long tetramer. Each spectrin filament interconnects to up to 5 other spectrins and is bound to the cell membrane via a protein complex consisting of protein 4.1R, actin, and glycophorin C (1). The plasma membrane fluctuations are related to RBCs' mechanical properties that have been extensively studied over the past three decades (2-6). It is well known that fluctuations of the membrane depend on its bending rigidity and its membrane tension (7). Furthermore, RBCs gain their elasticity from the elastic shear modulus of the cytoskeletal spectrin network (8, 9). Recent theoretical analysis (10) suggest that the spectrin cytoskeleton acts as a steric barrier restricting membrane undulations toward the network.Experiments by Tuvia and coworkers showed an ATP dependent effect by monitoring the static fluctuation amplit...

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“…7 erythrocyte viscosity was constant between pH 6 (apparent intracellular pH = 6.30) and pH 8 (apparenit intracellular pH = 7.80), but increased dramatically at pH 5 (apparent intracellular pH = 5.32). Since the viscosity of hemiioglobin solutions at conicentrations approachinig those in the erythrocyte are four to five orders of magnitude less (29) than the estimated bulk viscositv of the membrane (30), this increase in erythrocyte viscosity is likely due, in part, to diminished miiemiibrane deformability. This conclusioni is supported by the observation that uinsealed ghosts isolated fromii erythrocytes exposed to pH 5 show a similar increase in viscosity (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…But measurements of spectrin extraction from fresh and ATP-depleted ghosts as a function of extraction time showed that the decrease in spectrin extractability in the ATP-depleted sample, compared to normal, was evident throughout the extraction period. Extraction of spectrin from both samples reached a plateau by [20][21][22][23][24][25][26][27][28][29][30] h, well in advance of the time (40 h) when extractions were usually terminated (data not shown).…”

Section: Resultsmentioning

confidence: 99%

Diminished spectrin extraction from ATP-depleted human erythrocytes. Evidence relating spectrin to changes in erythrocyte shape and deformability.

Lux¹,

John²,

Ukena³

1978

J. Clin. Invest.

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A B S T R A C T We measured spectrin "extractal)ilitvy in erythrocytes which were metabolically depleted ly ineubatioin at 37°C in plasma or glucose-free buffers. Membranes were extracted with 1 mnl EDTA (pH 8, 40 h, 4°C) 12 September 1977. exposed to extremes of pH and temlperature. WVhen the pH in the ervthrocvte interior fell below 5.5, a pH where spectrini was aggregated and isoelectricallv precipitated, erythrocyte and ghost viscosity increased coincident with a marked decrease in spectrini extractability. Similarly above 49°C, a temperatture where spectrin was denatured and precipitated, ervthrocvte viscosity rose as inextractable spectrin a(-cumulated. These observations provide direct evidence of a chanige in the physical state of spectrini associated with a change in ervthrocvte shape and deformability. They sutpport the concept that erythrocyte shape and deformability are largely determiined by the shape aind deformal)ilitv of the spectrin-actiii protein meshwork which laminates the inner membrane surface.

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Rheological Comparison of Hemoglobin Solutions and Erythrocyte Suspensions

Cited by 169 publications

References 7 publications

Abnormal rheology of oxygenated blood in sickle cell anemia

Abnormal rheology of oxygenated blood in sickle cell anemia

ATP-dependent mechanics of red blood cells

Diminished spectrin extraction from ATP-depleted human erythrocytes. Evidence relating spectrin to changes in erythrocyte shape and deformability.

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