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Shear dependent red blood cell adhesion in microscale flow.

ABSTRACT: Non-adherence and deformability are the key intrinsic biomechanical features of the red blood cell (RBC), which allow it to tightly squeeze and pass through even the narrowest of microcirculatory networks. Blockage of microcirculatory flow, also known as vaso-occlusion, is a consequence of abnormal cellular adhesion to the vascular endothelium. In sickle cell disease (SCD), an inherited anaemia, even though RBCs have been shown to be heterogeneous in adhesiveness and deformability, this has not been studied in the context of physiologically relevant dynamic shear gradients at the microscale. We developed a microfluidic system that simulates physiologically relevant shear gradients of microcirculatory blood flow at a constant single volumetric flow rate. Using this system, shear dependent adhesion of RBCs from 28 subjects with SCD and from 11 healthy subjects was investigated using vascular endothelial protein functionalized microchannels. We defined a new term, RBC Shear Gradient Microfluidic Adhesion (SiGMA) index to assess shear dependent RBC adhesion in a subject-specific manner. We have shown for the first time that shear dependent adhesion of RBCs is heterogeneous in a microfluidic flow model, which correlates clinically with inflammatory markers and iron overload in subjects with SCD. This study reveals the complex dynamic interactions between RBC-mediated microcirculatory occlusion and clinical outcomes in SCD. These interactions may also be relevant to other microcirculatory disorders and microvascular diseases.

SUBMITTER: Kucukal E

PROVIDER: S-EPMC6421573 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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Shear dependent red blood cell adhesion in microscale flow.

Kucukal Erdem E Little Jane A JA Gurkan Umut A UA

Integrative biology : quantitative biosciences from nano to macro 20180401 4

Non-adherence and deformability are the key intrinsic biomechanical features of the red blood cell (RBC), which allow it to tightly squeeze and pass through even the narrowest of microcirculatory networks. Blockage of microcirculatory flow, also known as vaso-occlusion, is a consequence of abnormal cellular adhesion to the vascular endothelium. In sickle cell disease (SCD), an inherited anaemia, even though RBCs have been shown to be heterogeneous in adhesiveness and deformability, this has not ...[more]

PMID: 29557482

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Project description:In this work, we compared the dynamics of motion in a linear shear flow of individual red blood cells (RBCs) from healthy and pathological donors (Sickle Cell Disease (SCD) or Sickle Cell-β-thalassemia) and of low and high densities, in a suspending medium of higher viscosity. In these conditions, at lower shear rates, biconcave discocyte-shaped RBCs present an unsteady flip-flopping motion, where the cell axis of symmetry rotates in the shear plane, rocking to and fro between an orbital angle ±ϕ observed when the cell is on its edge. We show that the evolution of ϕ depends solely on RBC density for healthy RBCs, with denser RBCs displaying lower ϕ values than the lighter ones. Typically, at a shear stress of 0.08 Pa, ϕ has values of 82 and 72° for RBCs with average densities of 1.097 and 1.115, respectively. Surprisingly, we show that SCD RBCs display the same ϕ-evolution as healthy RBCs of same density, showing that the flip-flopping behavior is unaffected by the SCD pathology. When the shear stress is increased further (above 0.1 Pa), healthy RBCs start going through a transition to a fluid-like motion, called tank-treading, where the RBC has a quasi-constant orientation relatively to the flow and the membrane rotates around the center of mass of the cell. This transition occurs at higher shear stresses (above 0.2 Pa) for denser cells. This shift toward higher stresses is even more remarkable in the case of SCD RBCs, showing that the transition to the tank-treading regime is highly dependent on the SCD pathology. Indeed, at a shear stress of 0.2 Pa, for RBCs with a density of 1.097, 100% of healthy RBCs have transited to the tank-treading regime vs. less than 50% SCD RBCs. We correlate the observed differences in dynamics to the alterations of RBC mechanical properties with regard to density and SCD pathology reported in the literature. Our results suggest that it might be possible to develop simple non-invasive assays for diagnosis purpose based on the RBC motion in shear flow and relying on this millifluidic approach.

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Shear dependent red blood cell adhesion in microscale flow.

Publications

Shear dependent red blood cell adhesion in microscale flow.

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