Drug delivery by micro- and nano-carriers enables controlled transport of pharmaceuticals to targeted sites. Even though carrier fabrication has made much progress recently, the delivery including ...controlled particle distribution and adhesion within the body remains a great challenge. The adhesion of carriers is strongly affected by their margination properties (migration toward walls) in the microvasculature. To investigate margination characteristics of carriers of different shapes and sizes and to elucidate the relevant physical mechanisms, we employ mesoscopic hydrodynamic simulations of blood flow. Particle margination is studied for a wide range of hematocrit values, vessel sizes, and flow rates, using two- and three-dimensional models. The simulations show that the margination properties of particles improve with increasing carrier size. Spherical particles yield slightly better margination than ellipsoidal carriers; however, ellipsoidal particles exhibit a slower rotational dynamics near a wall favoring their adhesion. In conclusion, micron-sized ellipsoidal particles are favorable for drug delivery in comparison with sub-micron spherical particles.
The motion of red blood cells (RBCs) in microcirculation plays an important role in blood flow resistance and in the cell partitioning within a microvascular network. Different shapes and dynamics of ...RBCs in microvessels have been previously observed experimentally including the parachute and slipper shapes. We employ mesoscale hydrodynamic simulations to predict the phase diagram of shapes and dynamics of RBCs in cylindrical microchannels, which serve as idealized microvessels, for a wide range of channel confinements and flow rates. A rich dynamical behavior is found, with snaking and tumbling discocytes, slippers performing a swinging motion, and stationary parachutes. We discuss the effects of different RBC states on the flow resistance, and the influence of RBC properties, characterized by the Föppl-von Kármán number, on the shape diagram. The simulations are performed using the same viscosity for both external and internal fluids surrounding a RBC; however, we discuss how the viscosity contrast would affect the shape diagram.
Red blood cells, or erythrocytes, are seen to flicker under optical microscopy, a phenomenon initially described as thermal uctuations of the cell membrane. But recent studies have suggested the ...involvement of non-equilibrium processes, without denitively ruling out equilibrium interpretations. Using active and passive microrheology to directly compare the membrane response and uctuations on single erythrocytes, we report here a violation of the uctuationdissipation relation, which is a direct demonstration of the non-equilibrium nature of ickering. With an analytical model of the composite erythrocyte membrane and realistic stochastic simulations, we show that several molecular mechanisms may explain the active uctuations, and we predict their kinetics. We demonstrate that tangential metabolic activity in the network formed by spectrin, a cytoskeletal protein, can generate curvature-mediated active membrane motions. We also show that other active membrane processes represented by direct normal force dipoles may explain the observed membrane activity. Our ndings provide solid experimental and theoretical frameworks for future investigations of the origin and function of active motion in cells.
A recent study of red blood cells (RBCs) in shear flow Lanotte et al., Proc. Natl. Acad. Sci. U.S.A. 113, 13289 (2016)PNASA60027-842410.1073/pnas.1608074113 has demonstrated that RBCs first tumble, ...then roll, transit to a rolling and tumbling stomatocyte, and finally attain polylobed shapes with increasing shear rate, when the viscosity contrast between cytosol and blood plasma is large enough. Using two different simulation techniques, we construct a state diagram of RBC shapes and dynamics in shear flow as a function of shear rate and viscosity contrast, which is also supported by microfluidic experiments. Furthermore, we illustrate the importance of RBC shear elasticity for its dynamics in flow and show that two different kinds of membrane buckling trigger the transition between subsequent RBC states.
Proper functioning of white blood cells is not possible without their ability to adhere to vascular endothelium, which may occur only if they are close enough to vessel walls. To facilitate the ...adhesion, white blood cells migrate toward the vessel walls in blood flow through a process called margination. The margination of white cells depends on a number of conditions including local hematocrit, flow rate, red blood cell aggregation, and the deformability of both red and white cells. To better understand the margination process of white blood cells, we employ mesoscopic hydrodynamic simulations of a three-dimensional model of blood flow, which has been previously shown to capture quantitatively realistic blood flow properties and rheology. The margination properties of white blood cells are studied for a wide range of hematocrit values and flow conditions. Efficient white blood cell margination is found in an intermediate range of hematocrit values of Ht ≈ 0.2-0.4 and at relatively low flow rates, characteristic of the venular part of microcirculation. In addition, aggregation interactions between red blood cells lead to enhanced white-blood-cell margination. This simulation study provides a quantitative description of the margination of white blood cells, and is also highly relevant for the margination of particles or cells of similar size such as circulating tumor cells.
Mesoscale simulations of blood flow, where the red blood cells are described as deformable closed shells with a membrane characterized by bending rigidity and stretching elasticity, have made much ...progress in recent years to predict the flow behavior of blood cells and other components in various flows. To numerically investigate blood flow and blood-related processes in complex geometries, a highly efficient simulation technique for the plasma and solutes is essential. In this review, we focus on the behavior of single and several cells in shear and microcapillary flows, the shear-thinning behavior of blood and its relation to the blood cell structure and interactions, margination of white blood cells and platelets, and modeling hematologic diseases and disorders. Comparisons of the simulation predictions with existing experimental results are made whenever possible, and generally very satisfactory agreement is obtained.
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.
Predicting human blood viscosity in silico Fedosov, Dmitry A; Pan, Wenxiao; Caswell, Bruce ...
Proceedings of the National Academy of Sciences - PNAS,
07/2011, Letnik:
108, Številka:
29
Journal Article
Recenzirano
Odprti dostop
The viscosity of blood has long been used as an indicator in the understanding and treatment of disease, and the advent of modern viscometers allows its measurement with ever-improving clinical ...convenience. However, these advances have not been matched by theoretical developments that can yield a quantitative understanding of blood's microrheology and its possible connection to relevant biomolecules (e.g., fibrinogen). Using coarse-grained molecular dynamics and two different red blood cell models, we accurately predict the dependence of blood viscosity on shear rate and hematocrit. We explicitly represent cell-cell interactions and identify the types and sizes of reversible rouleaux structures that yield a tremendous increase of blood viscosity at low shear rates. We also present the first quantitative estimates of the magnitude of adhesive forces between red cells. In addition, our simulations support the hypothesis, previously deduced from experiments, of yield stress as an indicator of cell aggregation. This non-Newtonian behavior is analyzed and related to the suspension's microstructure, deformation, and dynamics of single red blood cells. The most complex cell dynamics occurs in the intermediate shear rate regime, where individual cells experience severe deformation and transient folded conformations. The generality of these cell models together with single-cell measurements points to the future prediction of blood-viscosity anomalies and the corresponding microstructures associated with various diseases (e.g., malaria, AIDS, and diabetes mellitus). The models can easily be adapted to tune the properties of a much wider class of complex fluids including capsule and vesicle suspensions.
Microvascular blood flow resistance has a strong impact on cardiovascular function and tissue perfusion. The flow resistance in microcirculation is governed by flow behavior of blood through a ...complex network of vessels, where the distribution of red blood cells across vessel cross-sections may be significantly distorted at vessel bifurcations and junctions. In this paper, the development of blood flow and its resistance starting from a dispersed configuration of red blood cells is investigated in simulations for different hematocrit levels, flow rates, vessel diameters, and aggregation interactions between red blood cells. Initially dispersed red blood cells migrate toward the vessel center leading to the formation of a cell-free layer near the wall and to a decrease of the flow resistance. The development of cell-free layer appears to be nearly universal when scaled with a characteristic shear rate of the flow. The universality allows an estimation of the length of a vessel required for full flow development, lc≲25D, for vessel diameters in the range 10 μm<D<100μm. Thus, the potential effect of red blood cell dispersion at vessel bifurcations and junctions on the flow resistance may be significant in vessels which are shorter or comparable to the length lc. Aggregation interactions between red blood cells generally lead to a reduction of blood flow resistance. The simulations are performed using the same viscosity for both external and internal fluids and the RBC membrane viscosity is not considered; however, we discuss how the viscosity contrast may affect the results. Finally, we develop a simple theoretical model which is able to describe the converged cell-free-layer thickness at steady-state flow with respect to flow rate. The model is based on the balance between a lift force on red blood cells due to cell-wall hydrodynamic interactions and shear-induced effective pressure due to cell–cell interactions in flow. We expect that these results can also be used to better understand the flow behavior of other suspensions of deformable particles such as vesicles, capsules, and cells.
•Microvascular blood flow resistance is affected by the distribution of red blood cells.•Red blood cell migration under various flow conditions has been quantified.•The length of a vessel required for the full development of cell-free layer is shorter than 25vesseldiameters.•A theoretical model for the converged cell-free layer thickness has been developed.
Clustering of flagellated microswimmers such as sperm is often mediated by hydrodynamic interactions between them. To better understand the interaction of microswimmers in viscoelastic fluids, we ...perform two-dimensional simulations of two swimming sheets, using a viscoelastic version of the smoothed dissipative particle dynamics method that implements the Oldroyd-B fluid model. Elasticity of sheets (stiff versus soft) defines two qualitatively different regimes of clustering, where stiff sheets exhibit a much more robust clustering than soft sheets. A formed doublet of soft sheets generally swims faster than a single swimmer, while a pair of two stiff sheets normally shows no speed enhancement after clustering. A pair of two identical swimmers is stable for most conditions, while differences in the beating amplitudes and/or frequencies between the two sheets can destroy the doublet stability. Clustering of two distinct swimmers is most stable at Deborah numbers of De =
≈ 1 (
is the relaxation time of a viscoelastic fluid and
is the beating frequency), in agreement with experimental observations. Therefore, the clustering of two swimmers depends non-monotonically on De. Our results suggest that the cluster stability is likely a dominant factor which determines the cluster size of collectively moving flagellated swimmers.
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