We measure the dynamical mechanical properties of human red blood cells. Single cell response is measured with optical tweezers. We investigate both the stress relaxation following a fast deformation, and the effect of varying the strain rate. We find a power law decay of the stress as a function of time, down to a plateau stress, and a power law increase of the cell's elasticity as a function of the strain rate. Interestingly, the exponents of these quantities violate the linear superposition principle, indicating a nonlinear response. We propose that this is due to breaking of a fraction of the crosslinks during the deformation process. The Soft Glassy Rheology Model accounts for the relation between the exponents we observe experimentally. This picture is consistent with recent models of bond remodeling in the red blood cell's molecular structure. Our results imply that the blood cell's mechanical behavior depends critically on the deformation process.
We use mesoscale numerical simulations to investigate the unsteady dynamics of a single red blood cell (RBC) subjected to an external mechanical load. We carry out a detailed comparison between the {\it loading} (L) dynamics, following the imposition of the mechanical load on the RBC at rest, and the {\it relaxation} (R) dynamics, allowing the RBC to relax to its original shape after the sudden arrest of the mechanical load. Such a comparison is carried out by analyzing the characteristic times of the two corresponding dynamics, i.e., $t_L$ and $t_R$. When the intensity of the mechanical load …
Viscoelastic transient of confined Red Blood Cells
红细胞在极小的微毛细管中流动的独特能力取决于其膜的粘弹性。在这里，我们在体外研究的响应时间后，流动启动所表现出的红细胞局限于微通道。我们表明，特征瞬态时间取决于施加的流动强度，并且这种依赖性提供了访问控制红细胞的时间响应的有效粘度和弹性模量。我们的实验数据的一个简单的理论分析，通过数值模拟验证，进一步使我们能够计算估计的二维膜粘度的红细胞，$η_{mem}^{2D}\sim 10^{-7}$ N $\cdot$ s $\cdot$ m $^{-1}$。通过比较我们的结果与以前的研究，我们讨论并澄清了文献中发现的关于$η_{mem}^{2D}$的测定的差异的起源，并调和了以前的作品似乎相互矛盾的结论。
In this work, we review previously developed coarse-grained (CG) particle models for biological membrane and red blood cells (RBCs) and discuss the advantages of the CG particle method over the continuum and atomic simulations on modeling biological phenomena. CG particle models can largely increase the length scale and time scale of atomic simulations by eliminating fast degrees of freedom while preserving the mesoscopic structures and properties of the simulated system. One the other hand, CG particle models can be used to capture microstructural alternations in diseased RBCs and simulate to…
Optimal hematocrit $H_o$ maximizes oxygen transport. In healthy humans, the average hematocrit $H$ is in the range of 40-45$\%$, but it can significantly change in blood pathologies such as severe anemia (low $H$) and polycythemia (high $H$). Whether the hematocrit level in humans corresponds to the optimal one is a long standing physiological question. Here, using numerical simulations with the Lattice Boltzmann method and two mechanical models of the red blood cell (RBC) we predict the optimal hematocrit, and explore how altering the mechanical properties of RBCs affects $H_o$. We develop a …
Blood exhibits a heterogeneous nature of hematocrit, velocity, and effective viscosity in microcapillaries. Microvascular bifurcations have a significant influence on the distribution of the blood cells and blood flow behavior. This paper presents a simulation study performed on the two-dimensionalmotions and deformation of multiple red blood cells in microvessels with diverging and converging bifurcations. Fluid dynamics and membrane mechanics were incorporated. Effects of cell shape, hematocrit, and deformability of the cell membrane on rheological behavior of the red blood cells and the hem…
We use numerical simulations to study the dynamics of red blood cells (RBCs) in unconfined and confined Poiseuille flow. Previous numerical studies with 3D vesicles have indicated that the slipper shape observed in experiments at high capillary number can be attributed to the bistability due to the interplay of wall push and outward migration tendency at higher viscosity contrasts. In this paper, we study this outward migration and bistability using numerical simulations for 3D capsules and provide phase diagrams of RBC dynamics with and without viscosity contrast. We observe a bistability of …
Constrictions in blood vessels and microfluidic devices can dramatically change the spatial distribution of passing cells or particles and are commonly used in biomedical cell sorting applications. However, the three-dimensional nature of cell focusing in the channel cross-section remains poorly investigated. Here, we explore the cross-sectional distribution of living and rigid red blood cells passing a constricted microfluidic channel by tracking individual cells in multiple layers across the channel depth and across the channel width. While cells are homogeneously distributed in the channel …
We study deformability-based sorting of same-size RBCs via DLD using an in-house integral equation solver. Our goal is to quantitatively characterize the physical mechanisms that enable the cell separation. To this end, we systematically investigate the effects of the interior fluid viscosity and membrane elasticity of a cell on its behavior. In particular, we consider deep devices in which a cell can show rich dynamics such as taking a particular angular orientation depending on its mechanical property. We have found out that cells moving with a sufficiently high positive inclination angle wi…
We present a new method for the geometric reconstruction of elastic surfaces simulated by the immersed boundary method with the goal of simulating the motion and interactions of cells in whole blood. Our method uses parameter-free radial basis functions for high-order meshless parametric reconstruction of point clouds and the elastic force computations required by the immersed boundary method. This numerical framework allows us to consider the effect of endothelial geometry and red blood cell motion on the motion of platelets. We find red blood cells to be crucial for understanding the motion …
An exhaustive description of the dynamics under shear flow of a large number of red blood cells in dilute regime is proposed, which highlights and takes into account the dispersion in cell properties within a given blood sample. Physiological suspending fluid viscosity is considered, a configuration surprisingly seldom considered in experimental studies, as well as a more viscous fluid that is a reference in the literature. Stable and unstable flipping motions well described by Jeffery orbits or modified Jeffery orbits are identified, as well as transitions to and from tank-treading motion in …
We present experiments on RBCs that flow through microcapillaries under physiological conditions. We show that the RBC clusters form as a subtle imbrication between hydrodynamics interaction and adhesion forces because of plasma proteins. Clusters form along the capillaries and macromolecule-induced adhesion contribute to their stability. However, at high yet physiological flow velocities, shear stresses overcome part of the adhesion forces, and cluster stabilization due to hydrodynamics becomes stronger. For the case of pure hydrodynamic interaction, cell-to-cell distances have a pronounced b…
Blood flow in sickle cell disease (SCD) can substantially differ from normal blood flow due to significant alterations in the physical properties of the red blood cells (RBCs). Chronic complications, such as inflammation of the endothelial cells lining blood vessel walls, are associated with SCD, for reasons that are unclear. Here, detailed boundary integral simulations are performed to investigate an idealized model flow flow in SCD, a binary suspension of flexible biconcave discoidal fluid-filled capsules and stiff curved prolate capsules that represent healthy and sickle RBCs, respectively,…
Flux of rigid or soft particles (such as drops, vesicles, red blood cells, etc.) in a channel is a complex function of particle concentration, which depends on the details of induced dissipation and suspension structure due to hydrodynamic interactions with walls or between neighboring particles. Through two-dimensional and three-dimensional simulations and a simple model that reveals the contribution of the main characteristics of the flowing suspension, we discuss the existence of an optimal volume fraction for cell transport and its dependence on the cell mechanical properties. The example …
The dynamics of single red blood cells (RBCs) determine microvascular blood flow by adapting their shape to the flow conditions in the narrow vessels. In this study, we explore the dynamics and shape transitions of RBCs on the cellular scale under confined and unsteady flow conditions using a combination of microfluidic experiments and numerical simulations. Tracking RBCs in a comoving frame in time-dependent flows reveals that the mean transition time from the symmetric croissant to the off-centered, non-symmetric slipper shape is significantly faster than the opposite shape transition, which…
On the rheology of red blood cell suspensions with different amounts of dextran: separating the effect of aggregation and increase in viscosity of the suspending phase
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.…
