Full dynamics of a red blood cell in shear flow

Abstract

At the cellular scale, blood fluidity and mass transport depend on the dynamics of red blood cells in blood flow, specifically on their deformation and orientation. These dynamics are governed by cellular rheological properties, such as internal viscosity and cytoskeleton elasticity. In diseases in which cell rheology is altered genetically or by parasitic invasion or by changes in the microenvironment, blood flow may be severely impaired. The nonlinear interplay between cell rheology and flow may generate complex dynamics, which remain largely unexplored experimentally. Under simple shear flow, only two motions, "tumbling" and "tank-treading," have been described experimentally and relate to cell mechanics. Here, we elucidate the full dynamics of red blood cells in shear flow by coupling two videomicroscopy approaches providing multidirectional pictures of cells, and we analyze the mechanical origin of the observed dynamics. We show that contrary to common belief, when red blood cells flip into the flow, their orientation is determined by the shear rate. We discuss the "rolling" motion, similar to a rolling wheel. This motion, which permits the cells to avoid energetically costly deformations, is a true signature of the cytoskeleton elasticity. We highlight a hysteresis cycle and two transient dynamics driven by the shear rate: an intermittent regime during the "tank-treading-to-flipping" transition and a Frisbee-like "spinning" regime during the "rolling-to-tank-treading" transition. Finally, we reveal that the biconcave red cell shape is highly stable under moderate shear stresses, and we interpret this result in terms of stress-free shape and elastic buckling. . Its fluidity strongly depends on its behavior in flow, which is a key factor of proper tissue perfusion. At the cellular scale, blood flow behavior is affected primarily by the RBC response to the hydrodynamic stress in terms of cell orientation relative to the flow direction and of cell deformation. For example, on one hand, at low shear rates, similar cell orientations may favor the formation of stacks (rouleaux) (1) of RBCs, like rolls of coins, which increases blood viscosity. On the other hand, at high shear rates, the individualization of RBCs, their alignment, and their stretching in the flow (2) decrease blood viscosity (3). The orientation and the deformation in flow of RBCs are governed by their rheological properties. They result from the viscoelastic contributions of all components of the cell composite structure. Moreover, RBC rheological properties also depend on the microenvironment and on metabolic functionality (4). Both local and systemic disturbances of homeostasis (in diabetes mellitus, hypertension) have the potential to induce RBC rheological alterations and consequently to impair blood circulation. It therefore is crucial to understand the relationships between the rheological properties of RBCs and their orientation and deformation in flow. This question is far from trivial because even in a simple shear flow, RBCs present a v...

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

“…For increasing shear rates up to 10 s −1 , more and more cells are found to roll on their edge, as previously observed in experiments using rheoscopes (24) and more recently in flow chambers (18,25). Shear thinning in this range of shear rates is therefore mainly controlled by discocyte orientation.…”

“…Recent experiments realized on dilute RBC suspensions with outer viscosities similar to that of the hemoglobin-rich cytoplasm have demonstrated, however, that the solid-like tumbling motion is not replaced by tank treading for increasing shear rates, but rather by a typical solid rolling motion, where the axis of symmetry of the discocyte lies in the direction of vorticity (18). Even for shear stresses up to 0.5 Pa no fluidization of the membrane was observed, demonstrating the important role the inner-to-outer viscosity ratio λ plays on local dynamics.…”

Microscale flow propulsion through bioinspired and magnetically actuated artificial cilia

“…Hemodynamics in microcirculation is important to the etiology of hemorheology and circulatory diseases. 18,19 In microvessels with diameters below 200 lm, the assumption of homogeneous continuum is no longer valid, and the rheological properties of individual red blood cell (RBC) become relevant to the physiology and pathologies of the microcirculatory system. 20 The transient dynamics of RBCs are predominantly affected by the shear stress in the flow.…”

“…20 The transient dynamics of RBCs are predominantly affected by the shear stress in the flow. 18 Under the influence of a shear flow applied by the local and systematic disturbances of hemostasis, RBCs can present various dynamic states, such as steady tank-treading, swinging, unsteady tumbling, and chaotic motion, which may lead to detrimental effects on the blood circulation. 18 The influences of these changes in RBC orientation and deformation give rise to additional concerns regarding the design of a micro total analysis system, in which the hemodynamics of individual RBC should be evaluated and assessed in a microfluidic platform for early detection of pathological flow symptoms in the blood flow.…”

“…18 Under the influence of a shear flow applied by the local and systematic disturbances of hemostasis, RBCs can present various dynamic states, such as steady tank-treading, swinging, unsteady tumbling, and chaotic motion, which may lead to detrimental effects on the blood circulation. 18 The influences of these changes in RBC orientation and deformation give rise to additional concerns regarding the design of a micro total analysis system, in which the hemodynamics of individual RBC should be evaluated and assessed in a microfluidic platform for early detection of pathological flow symptoms in the blood flow. 21 Recent studies also indicated that in the inner lining of a blood vessel wall, endothelial cells play an important role in regulating downstream intracellular responses and modulating the gene/protein expression pathway through the conversion of the wall shear stress load to biochemical signals.…”