Red cells’ dynamic morphologies govern blood shear thinning under microcirculatory flow conditions

Abstract

Blood viscosity decreases with shear stress, a property essential for an efficient perfusion of the vascular tree. Shear thinning is intimately related to the dynamics and mutual interactions of RBCs, the major component of blood. Because of the lack of knowledge about the behavior of RBCs under physiological conditions, the link between RBC dynamics and blood rheology remains unsettled. We performed experiments and simulations in microcirculatory flow conditions of viscosity, shear rates, and volume fractions, and our study reveals rich RBC dynamics that govern shear thinning. In contrast to the current paradigm, which assumes that RBCs align steadily around the flow direction while their membranes and cytoplasm circulate, we show that RBCs successively tumble, roll, deform into rolling stomatocytes, and, finally, adopt highly deformed polylobed shapes for increasing shear stresses, even for semidilute volume fractions of the microcirculation. Our results suggest that any pathological change in plasma composition, RBC cytosol viscosity, or membrane mechanical properties will affect the onset of these morphological transitions and should play a central role in pathological blood rheology and flow behavior.

High-throughput microfluidic characterization of erythrocyte shape and mechanical variability

“…This is due to the fact that high viscosity contrasts suppress membrane tank-treading, thereby making the slipper state unfavorable. In fact, RBCs at λ = 5 in simple shear flow do not exhibit tank-treading motion at all (9,36). However, under strong confinement, membrane tank-treading becomes possible, as we observe slippers in the diagram in Fig.…”

“…Empirical approximation of the inherent variation in RBC shear elasticity leads to RBC state distributions, which agree well with experimental observations. Furthermore, the experiments show the existence of tumbling polylobe shapes in large enough channels at high flow rates, which were before only observed in pure shear flow (9,36). The combination of experimental and simulation results allows us to fill several gaps in understanding of RBC behavior in microchannels and to make a step toward a quantitative characterization of RBC mechanical properties and their variability.…”

“…2I). Polylobe shapes were observed at high shear rates in simple shear flow both experimentally and numerically (9,36).…”

“…Additionally, the presence of membrane viscosity, which was not modeled in simulations, would further increase the viscous resistance for cell deformation (56,57). A high viscosity contrast is known to prohibit tank-treading motion of vesicles (58,59) and RBCs (9,36) in pure shear flow. Similarly, RBC tank-treading in a channel may be hindered by a high enough viscosity contrast, resulting in a polylobe.…”

“…The ability to deform and change shape is vital for RBCs, as they pass vessels whose diameter is smaller than their own size (1,2). Changes in elastic properties and shape of RBCs are of great interest in microcirculation research, because they affect many essential microvascular processes, including blood flow resistance (3)(4)(5), the viscosity of whole blood (6)(7)(8)(9), ATP release and oxygen delivery (10)(11)(12). Alterations in RBC material properties and shape are often associated with different blood diseases and disorders (13,14), such as sickle cell anemia (15,16), diabetes mellitus (17,18), and malaria (19)(20)(21).…”