Numerical simulation of red blood cell distributions in three-dimensional microvascular bifurcations

Hyakutake, Toru; Nagai, Shinya

doi:10.1016/j.mvr.2014.10.001

Cited by 48 publications

(29 citation statements)

References 34 publications

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“…The present assumption is also consistent with the previous knowledge on the Fåhraeus effect. It is noteworthy that these methodological advances take place while, in parallel, efficient simulation methods are emerging to study phase separation of multi-RBC systems in small channels in three dimensions, 14,18,25 which is also highly challenging. 11 We believe that, in the future, cross-fertilization between these experimental and computational approaches will lead to fantastic breakthroughs, the experiments providing insight on the phenomenology and reference data needed to validate the simulations and calibrate their input parameters, and the simulations enabling the study of situations that cannot be experimentally reproduced or of parameters that cannot be experimentally measured, e.g., the trajectory of individual RBCs or the mean velocity profile of the suspending fluid.…”

Section: Discussionmentioning

confidence: 99%

Going beyond 20 μm-sized channels for studying red blood cell phase separation in microfluidic bifurcations

et al. 2016

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Despite the development of microfluidics, experimental challenges are considerable for achieving a quantitative study of phase separation, i.e., the non-proportional distribution of Red Blood Cells (RBCs) and suspending fluid, in microfluidic bifurcations with channels smaller than 20 lm. Yet, a basic understanding of phase separation in such small vessels is needed for understanding the coupling between microvascular network architecture and dynamics at larger scale. Here, we present the experimental methodologies and measurement techniques developed for that purpose for RBC concentrations (tube hematocrits) ranging between 2% and 20%. The maximal RBC velocity profile is directly measured by a temporal cross-correlation technique which enables to capture the RBC slip velocity at walls with high resolution, highlighting two different regimes (flat and more blunted ones) as a function of RBC confinement. The tube hematocrit is independently measured by a photometric technique. The RBC and suspending fluid flow rates are then deduced assuming the velocity profile of a Newtonian fluid with no slip at walls for the latter. The accuracy of this combination of techniques is demonstrated by comparison with reference measurements and verification of RBC and suspending fluid mass conservation at individual bifurcations. The present methodologies are much more accurate, with less than 15% relative errors, than the ones used in previous in vivo experiments. Their potential for studying steady state phase separation is demonstrated, highlighting an unexpected decrease of phase separation with increasing hematocrit in symmetrical, but not asymmetrical, bifurcations and providing new reference data in regimes where in vitro results were previously lacking. Published by AIP Publishing. [http://dx

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Section: Discussionmentioning

confidence: 99%

Going beyond 20 μm-sized channels for studying red blood cell phase separation in microfluidic bifurcations

et al. 2016

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“…During their travel in the microcirculation, they experience a cascade of branching vessels. Many numerical studies have been performed in single or multiple bifurcations regarding more or less complex models of blood flow (36)(37)(38)(39)(40)(41). The arterioles are wrapped by smooth muscle cells and are well innervated, so in principle they are capable of controlling their pressure via vasomotion.…”

Section: Atp Release At and After A Bifurcationmentioning

confidence: 99%

ATP Release by Red Blood Cells under Flow: Model and Simulations

Zhang

Shen

Hogan

et al. 2018

Biophysical Journal

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ATP is a major player as a signaling molecule in blood microcirculation. It is released by red blood cells (RBCs) when they are subjected to shear stresses large enough to induce a sufficient shape deformation. This prominent feature of chemical response to shear stress and RBC deformation constitutes an important link between vessel geometry, flow conditions, and the mechanical properties of RBCs, which are all contributing factors affecting the chemical signals in the process of vasomotor modulation of the precapillary vessel networks. Several in vitro experiments have reported on ATP release by RBCs due to mechanical stress. These studies have considered both intact RBCs as well as cells within which suspected pathways of ATP release have been inhibited. This has provided profound insights to help elucidate the basic governing key elements, yet how the ATP release process takes place in the (intermediate) microcirculation zone is not well understood. We propose here an analytical model of ATP release. The ATP concentration is coupled in a consistent way to RBC dynamics. The release of ATP, or the lack thereof, is assumed to depend on both the local shear stress and the shape change of the membrane. The full chemomechanical coupling problem is written in a lattice-Boltzmann formulation and solved numerically in different geometries (straight channels and bifurcations mimicking vessel networks) and under two kinds of imposed flows (shear and Poiseuille flows). Our model remarkably reproduces existing experimental results. It also pinpoints the major contribution of ATP release when cells traverse network bifurcations. This study may aid in further identifying the interplay between mechanical properties and chemical signaling processes involved in blood microcirculation.Under shear flow, both vesicles (in two and three dimensions) and RBCs exhibit the following two main modes: TT (the cell or vesicle acquires a given orientation while the membrane rotates around the center of mass) and TB (a quasi-solid-like flipping). For vesicles, TB occurs at high enough internal fluid viscosity with respect to the external one, whereas TT prevails at low enough internal viscosity (17). For RBCs (18-21), the transition from TB to TT can be achieved by increasing shear stress. For low shear stress, RBCs exhibit TB, whereas for large shear stress, we have TT. Experiments Modeling ATP Release by RBCs under Flow

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“…C, D: High viscosity contrast (experiments with λ =10.3 and simulation with λ =10). effect where cells entering the bifurcation tend to be displaced towards the low flow rate branch compared to fluid streamlines (a fact that slightly reduces the Zweifach-Fung effect) (Barber et al, 2008;Doyeux et al, 2011;Li et al, 2012;Ollila et al, 2013), but this question is still debated (Hyakutake and Nagai, 2015;Xiong and Zhang, 2012).…”

Section: Simulation λ=1mentioning

confidence: 99%

Inversion of hematocrit partition at microfluidic bifurcations

Shen

Coupier

Kaoui

et al. 2016

Microvascular Research

100

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Partitioning of red blood cells (RBCs) at the level of bifurcations in the microcirculatory system affects many physiological functions yet it remains poorly understood. We address this problem by using T-shaped microfluidic bifurcations as a model. Our computer simulations and in vitro experiments reveal that the hematocrit (ϕ0) partition depends strongly on RBC deformability, as long as ϕ0<20% (within the normal range in microcirculation), and can even lead to complete deprivation of RBCs in a child branch. Furthermore, we discover a deviation from the Zweifach-Fung effect which states that the child branch with lower flow rate recruits less RBCs than the higher flow rate child branch. At small enough ϕ0, we get the inverse scenario, and the hematocrit in the lower flow rate child branch is even higher than in the parent vessel. We explain this result by an intricate up-stream RBC organization and we highlight the extreme dependence of RBC transport on geometrical and cell mechanical properties. These parameters can lead to unexpected behaviors with consequences on the microcirculatory function and oxygen delivery in healthy and pathological conditions.

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Numerical simulation of red blood cell distributions in three-dimensional microvascular bifurcations

Cited by 48 publications

References 34 publications

Going beyond 20 μm-sized channels for studying red blood cell phase separation in microfluidic bifurcations

Going beyond 20 μm-sized channels for studying red blood cell phase separation in microfluidic bifurcations

ATP Release by Red Blood Cells under Flow: Model and Simulations

Inversion of hematocrit partition at microfluidic bifurcations

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