Targeting spectrin redox switches to regulate the mechanoproperties of red blood cells

AbstractThe mechanical properties of red blood cells (RBCs) are fundamental for their physiological role as gas transporters. RBC flexibility and elasticity allow them to survive the hemodynamic changes in the different regions of the vascular tree, to dynamically contribute to the flow thereby decreasing vascular resistance, and to deform during the passage through narrower vessels. RBC mechanoproperties are conferred mainly by the structural characteristics of their cytoskeleton, which consists predominantly of a spectrin scaffold connected to the membrane via nodes of actin, ankyrin and adducin. Changes in redox state and treatment with thiol-targeting molecules decrease the deformability of RBCs and affect the structure and stability of the spectrin cytoskeleton, indicating that the spectrin cytoskeleton may contain redox switches. In this perspective review, we revise current knowledge about the structural and functional characterization of spectrin cysteine redox switches and discuss the current lines of research aiming to understand the role of redox regulation on RBC mechanical properties. These studies may provide novel functional targets to modulate RBC function, blood viscosity and flow, and tissue perfusion in disease conditions.

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High-throughput assessment of mechanical properties of stem cell derived red blood cells, toward cellular downstream processing

Scientific Reports ◽

10.1038/s41598-017-14958-w ◽

2017 ◽

Vol 7 (1) ◽

Cited By ~ 13

Author(s):

Ewa Guzniczak ◽

Maryam Mohammad Zadeh ◽

Fiona Dempsey ◽

Melanie Jimenez ◽

Henry Bock ◽

...

Keyword(s):

Mechanical Properties ◽

Stem Cell ◽

Red Blood Cells ◽

High Throughput ◽

Blood Cells ◽

Downstream Processing

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The Physiological Role of the Lymphoid System. V. The Binding of Autologous (Erythrophilic) γ-Globulin to Human Red Blood Cells*

Biochemistry ◽

10.1021/bi00863a007 ◽

1967 ◽

Vol 6 (11) ◽

pp. 3378-3385 ◽

Cited By ~ 23

Author(s):

B. V. Fidalgo ◽

Y. Katayama ◽

V. A. Najjar

Keyword(s):

Red Blood Cells ◽

Blood Cells ◽

Physiological Role ◽

Human Red Blood Cells ◽

Lymphoid System

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Clock gene-independent daily regulation of haemoglobin oxidation in red blood cells

10.1101/2021.10.11.463714 ◽

2021 ◽

Author(s):

Andrew D. Beale ◽

Priya Crosby ◽

Utham K. Valekunja ◽

Rachel S. Edgar ◽

Johanna E. Chesham ◽

...

Keyword(s):

Circadian Rhythms ◽

Red Blood Cells ◽

Blood Cells ◽

Human Subjects ◽

Developmental Regulation ◽

Physiological Role ◽

Cell Types ◽

The Body

AbstractCellular circadian rhythms confer daily temporal organisation upon behaviour and physiology that is fundamental to human health and disease. Rhythms are present in red blood cells (RBCs), the most abundant cell type in the body. Being naturally anucleate, RBC circadian rhythms share key elements of post-translational, but not transcriptional, regulation with other cell types. The physiological function and developmental regulation of RBC circadian rhythms is poorly understood, however, partly due to the small number of appropriate techniques available. Here, we extend the RBC circadian toolkit with a novel biochemical assay for haemoglobin oxidation status, termed “Bloody Blotting”. Our approach relies on a redox-sensitive covalent haem-haemoglobin linkage that forms during cell lysis. Formation of this linkage exhibits daily rhythms in vitro, which are unaffected by mutations that affect the timing of circadian rhythms in nucleated cells. In vivo, haemoglobin oxidation rhythms demonstrate daily variation in the oxygen-carrying and nitrite reductase capacity of the blood, and are seen in human subjects under controlled laboratory conditions as well as in freely-behaving humans. These results extend our molecular understanding of RBC circadian rhythms and suggest they serve an important physiological role in gas transport.

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Mechanical Properties of Stored Red Blood Cells Using Optical Tweezers

Blood ◽

10.1182/blood.v92.8.2975 ◽

1998 ◽

Vol 92 (8) ◽

pp. 2975-2977 ◽

Cited By ~ 32

Author(s):

R.R. Huruta ◽

M.L. Barjas-Castro ◽

S.T.O. Saad ◽

F.F. Costa ◽

A. Fontes ◽

...

Keyword(s):

Mechanical Properties ◽

Red Blood Cells ◽

Optical Tweezers ◽

Blood Cells

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Determination of the Mechanical Properties of Red Blood Cells in Sickle Cell Disease

Microscopy and Microanalysis ◽

10.1017/s1431927620000471 ◽

2020 ◽

Vol 26 (S1) ◽

pp. 47-48

Author(s):

Georges Minatchy ◽

Laurence Romana ◽

Grégory Francius ◽

Marc Romana

Keyword(s):

Mechanical Properties ◽

Sickle Cell Disease ◽

Red Blood Cells ◽

Sickle Cell ◽

Blood Cells ◽

Cell Disease

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Sorting same-size red blood cells in deep deterministic lateral displacement devices

Journal of Fluid Mechanics ◽

10.1017/jfm.2018.829 ◽

2018 ◽

Vol 859 ◽

pp. 433-475 ◽

Cited By ~ 7

Author(s):

Gökberk Kabacaoğlu ◽

George Biros

Keyword(s):

Mechanical Properties ◽

Red Blood Cells ◽

Blood Cells ◽

Lateral Displacement ◽

Flow Direction ◽

Lateral Direction ◽

Deterministic Lateral Displacement ◽

Deformable Particles ◽

Dense Suspensions ◽

A Cell

Microfluidic sorting of deformable particles finds many applications, for example, medical devices for cells. Deterministic lateral displacement (DLD) is one of them. Particle sorting via DLD relies only on hydrodynamic forces. For rigid spherical particles, this separation is to a great extent understood and can be attributed to size differences: large particles displace in the lateral direction with respect to the flow while small particles travel in the flow direction with negligible lateral displacement. However, the separation of non-spherical deformable particles such as red blood cells (RBCs) is more complicated than that of rigid particles. For example, is it possible to separate deformable particles that have the same size but different mechanical properties? We study deformability-based sorting of same-size RBCs via DLD using an in-house integral equation solver for vesicle flows in two dimensions. Our goal is to quantitatively characterize the physical mechanisms that enable the cell separation. To this end, we systematically investigate the effects of the interior fluid viscosity and membrane elasticity of a cell on its behaviour. In particular, we consider deep devices in which a cell can show rich dynamics such as taking a particular angular orientation depending on its mechanical properties. We have found out that cells moving with a sufficiently high positive inclination angle with respect to the flow direction displace laterally while those with smaller angles travel with the flow streamlines. Thereby, deformability-based cell sorting is possible. The underlying mechanism here is cell migration due to the cell’s positive inclination and the shear gradient. The higher the inclination is, the farther the cell can travel laterally. We also assess the efficiency of the technique for dense suspensions. It turns out that most of the cells in dense suspensions do not displace in the lateral direction no matter what their deformability is. As a result, separating cells using a DLD device becomes harder.

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