Red blood cells (RBCs) -- erythrocytes -- suspended in plasma tend to aggregate and form rouleaux. During aggregation the first stage consists in the formation of RBC doublets [Blood cells, molecules, and diseases 25, 339 (1999)]. While aggregates are normally dissociated by moderate flow stresses, under some pathological conditions the aggregation becomes irreversible, which leads to high blood viscosity and vessel occlusion. We perform here two-dimensional simulations to study the doublet dynamics under shear flow in different conditions and its impact on rheology. We sum up our results on the dynamics of doublet in a rich phase diagram in the parameter space (flow strength, adhesion energy) showing four different types of doublet configurations and dynamics. We find that membrane tank-treading plays an important role in doublet disaggregation, in agreement with experiments on RBCs. A remarkable feature found here is that when a single cell performs tumbling (by increasing vesicle internal viscosity) the doublet formed due to adhesion (even very weak) remains stable even under a very strong shear rate. It is seen in this regime that an increase of shear rate induces an adaptation of the doublet conformation allowing the aggregate to resist cell-cell detachment. We show that the normalized effective viscosity of doublet suspension increases significantly with the adhesion energy, a fact which should affect blood perfusion in microcirculation.
In this work, we develop a two-component coarse-grained molecular dynamics (CGMD) model for simulating the erythrocyte membrane. This proposed model possesses the key feature of combing the lipid bilayer and the erythrocyte cytoskeleton, thus showing both the fluidic behavior of the lipid bilayer and elastic properties of the erythrocyte cytoskeleton. The proposed model facilitates simulations that span large length-scales (~ micrometer) and time-scales (~ ms). By tuning the interaction potential parameters, diffusivity and bending rigidity of the membrane model can be controlled. In the study…
The non-linear behavior of human erythrocytes subjected to shear stress was analyzed using data series from the Erythrocyte Rheometer and a theoretical model was developed. Linear behavior was eliminated by means of a slot filter and a sixth order Savisky-Golay filter was applied to the resulting time series that allows the elimination of any possible white noise in the data. A fast Fourier transform was performed on the processed data, which resulted in a series of frequency dominant peaks. Results suggest the presence of a non-linear quadratic term in the Kelvin-Voigt phenomenological model.…
Occlusive thrombosis in arteries causes heart attacks and strokes. The rapid growth of thrombus at elevated shear rates (~10,000 1/s) relies on shear-induced platelet aggregation (SIPA) thought to come about from the entanglement of von Willebrand factor (VWF) molecules. The mechanism for SIPA is not yet understood in terms of cell- and molecule-level dynamics in fast-flowing bloodstreams. Towards this end, we develop a multiscale computational model to recreate SIPA in silico, where the suspension dynamics and interactions of individual platelets and VWF multimers are resolved directly. The p…
Flowing blood displays a phenomenon called margination, in which leukocytes and platelets are preferentially found near blood vessel walls, while erythrocytes are depleted from these regions. Here margination is investigated using direct hydrodynamic simulations of a binary suspension of stiff (s) and floppy (f) capsules, as well as a stochastic model that incorporates the key particle transport mechanisms in suspensions -- wall-induced hydrodynamic migration and shear-induced pair collisions. The stochastic model allows the relative importance of these two mechanisms to be directly evaluated …
We investigate the shear thinning of red blood cell - dextran suspensions. Microscopic images show that at low polymer concentration, aggregation increases with increasing concentration until it reaches a maximum and then decreases again to non-aggregation. This bell shape dependency is also deduced from the rheological measurements, if the data are correctly normalized by the viscosity of the suspending phase since a significant amount of polymers adsorb to the cell surfaces. We find that the position of the maximum of this shear rate dependent bell shape increases with increasing viscosity o…
The reversible aggregation of red blood cells (RBCs) is a process of erythrocytes clumping that strongly influences the rheological properties of blood. The adhesion of RBCs has been studied extensively in the frame of cell-to-cell interaction induced by dextran macromolecules, whereas the data is lacking for native plasma solution. We apply optical tweezers to investigate the induced adhesion of RBCs in plasma and in dextran solution. Two hypotheses 'cross-bridges' and 'depletion layer' are being utilized to describe the mechanism of cells interaction, while both need to be confirmed experime…
The activity of growing living bacteria was investigated using real-time and in situ rheology -- in stationary and oscillatory shear. Two different strains of the human pathogen Staphylococcus aureus -- strain COL and its isogenic cell wall autolysis mutant -- were considered in this work. For low bacteria density, strain COL forms small clusters, while the mutant, presenting deficient cell separation, forms irregular larger aggregates. In the early stages of growth, when subjected to a stationary shear, the viscosity of both strains increases with the population of cells. As the bacteria reac…
The early stages of clot formation in blood vessels involve platelets adhesion-aggregation. Although these mechanisms have been extensively studied, gaps in their understanding still persist. We have performed detailed in-vitro experiments and developed a numerical model to better describe and understand this phenomenon. Unlike previous studies, we took into account both activated and non-activated platelets, as well as the 3D nature of the aggregation process. Our investigation reveals that blood albumin is a major parameter limiting platelet adhesion and aggregation. Our results also show th…
To avoid pathological platelet aggregation by von Willebrand factor (VWF), VWF multimers are regulated in size and reactivity for adhesion by ADAMTS13-mediated proteolysis in a shear flow dependent manner. We examined if tensile stress in VWF under shear flow activates the VWF A2 domain for cleavage by ADAMTS13 using molecular dynamics simulations. We indeed observed stepwise unfolding of A2 and exposure of its deeply buried ADAMTS13 cleavage site. Interestingly, disulfide bonds in the adjacent and highly homologous VWF A1 and A3 domains obstruct their mechanical unfolding. We generated a full…
Similarly to their biological counterparts, suspensions of chemically-active autophoretic swimmers exhibit nontrivial dynamics involving self-organization processes as a result of inter-particle interactions. Using a kinetic model for a dilute suspension of autochemotactic Janus particles, we analyse the effect of a confined pressure-driven flow on these collective behaviours and the impact of chemotactic aggregation on the effective viscosity of the active fluid. Four dynamic regimes are identified when increasing the strength of the imposed pressure-driven flow, each associated with a differ…
von Willebrand Factor is a mechano-sensitive protein circulating in blood that mediates platelet adhesion to subendothelial collagen and platelet aggregation at high shear rates. Its hemostatic function and thrombogenic effect, as well as susceptibility to enzymatic cleavage, are regulated by a conformational change from a collapsed globular state to a stretched state. Therefore, it is essential to account for the conformation of the vWF multimers when modeling vWF-mediated thrombosis or vWF degradation. We introduce a continuum model of vWF unfolding that is developed within the framework of …
Plasma proteins such as fibrinogen induce the aggregation of red blood cells (RBC) into rouleaux, which are responsible for the pronounced shear thinning behavior of blood, control the erythro- cyte sedimentation rate (ESR) a common hematological test and are involved in many situations of physiological relevance such as structuration of blood in the microcirculation or clot formation in pathological situations. Confocal microscopy is used to characterize the shape of RBCs within rouleaux at equilibrium as a function of macromolecular concentration, revealing the diversity of contact zone morp…
