Red blood cell and platelet diffusivity and margination in the presence of cross-stream gradients in blood flows

Abstract

The radial distribution of cells in blood flow inside vessels is highly non-homogeneous. This leads to numerous important properties of blood, yet the mechanisms shaping these distributions are not fully understood. The motion of cells is governed by a variety of hydrodynamic interactions and cell-deformation mechanics. Properties, such as the effective cell diffusivity, are therefore difficult to investigate in flows other than pure shear flows. In this work, several single-cell, cell-pair, and large-scale many-cell simulations are performed using a validated numerical model. Apart from the single-cell mechanical validations, the arising flow profile, cell free layer widths, and cell drift velocities are compared to previous experimental findings. The motion of the cells at various radial positions and under different flow conditions is extracted, and evaluated through a statistical approach. An extended diffusive flux-type model is introduced which describes the cell diffusivities under a wide range of flow conditions and incorporates the effects of cell deformability through a shear dependent description of the cell collision cross sections. This model is applicable for both red blood cells and platelets. Further evaluation of particle trajectories shows that the margination of platelets cannot be the net result of gradients in diffusivity. However, the margination mechanism is strongly linked to the gradient of the hematocrit level. Finally, it shows that platelets marginate only until the edge of the red blood cell distribution and they do not fill the cell free layer.

The influence of red blood cell deformability on hematocrit profiles and platelet margination

“…The diffusion coefficients were computed per radius region and averaged over 0.4 seconds, with a time window of 0.5ms. We follow the specific procedure from a previous study [33] and confirm that RBC radial diffusion increases from the center of the pipe towards the wall, following the increase of shear rate. Radial diffusivities are shown in the left panels of PLOS COMPUTATIONAL BIOLOGY simulations, an increase of RBC D rr in all regions of the pipe is observed.…”

“…HemoCell has been validated to reproduce the mechanical responses of an individual, healthy, RBC induced by sheared flow and optical tweezers, as well as accurately reproducing bulk flow hallmarks of whole blood such as the Fåhraeus-Lindqvist effect and the CFL [31]. With this validated RBC model HemoCell has been used to study the effects of RBC cytoplasmic viscosity contrasts in bulk flow [32], the role of hematocrit profiles on cell diffusivities in flow [33], as well as identifying the start of a platelet aggregate [40]. The capabilities of HemoCell allow the tracking of the individual suspended healthy RBCs, stiffened RBCs, and platelets that are present in the in vitro experiments reported in this study.…”

“…Following the same trend as the homogeneous RBC collisions which approach the time-reversible stokes regime as RBC stiffness increases. It should be noted that this effect is relatively small, and the platelet-RBC collision is mostly influenced by the disparity of size between the two [33]. Although there is a small effect of RBC stiffness with platelet displacement, RBC deformation is mostly negligible in any RBC stiffness scenario as the RBC is much larger, which contributes most to the displacement of the platelet.…”

“…Cell resolved numerical simulations are then performed to confirm the results of the experiments and investigate what cannot be captured by the experiment. We use the validated cell resolved blood flow model HemoCell [31][32][33][34], which is a Lattice Boltzmann method (LBM) for the blood plasma, and a discrete element method for the RBC material model that is coupled to the plasma via the immersed boundary method. With HemoCell, we first study the influence of RBC deformability on the cell-pair level with homogeneous and heterogeneous RBC-RBC collisions, as well as collisions between platelets and RBCs.…”

Biorheology of occlusive thrombi formation under high shear: in vitro growth and shrinkage

“…In our previous study, an increase in platelet flux of about two times in WB was found in comparison to PRP in Van Rooij’s flow chamber [van Rooij et al, submitted]. This increase is caused by enhanced diffusion due to the presence of red blood cells 32 . However, in PRP this enhanced diffusion is not present.…”