Abstract

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.

Highlights

  • The high deformability of red blood cells (RBCs) is an essential element of blood fluidity

  • The Mean Corpuscular Hemoglobin Concentration (MCHC) measured on the HbβS sample is the lowest among the seven blood samples, disclosing an Hb deficit within individual Sickle Cell-β-thalassemia RBCs

  • This estimated mean density correlated well with the MCHC measured on each blood sample, as displayed in Supplementary Figure 2 together with data collected from the literature, validating our approach to estimate the RBC amount in the density layers

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Summary

Introduction

The high deformability of red blood cells (RBCs) is an essential element of blood fluidity. It plays a role in the coupling between RBCs and flow and, in their individual dynamics, such as shape and orientation in the flow. Reduced cell deformability alters the ability of RBCs to change their overall shape to pass through the smallest capillaries of the microcirculation and the inter-endothelial slits in the spleen (Salehyar and Zhu, 2016; Gambhire et al, 2017; Safeukui et al, 2018). In sickle cell disease where RBC deformability decreases and their stickiness increases, the combined alterations potentially lead to thrombus formation and vaso-occlusive events in capillaries. It is important to be able to detect alterations of RBC deformability in health and disease

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