Temporal-spatial heterogeneity of hematocrit in microvascular networks

Li, Guansheng; Ye, Ting; Yang, Bo; Wang, Sitong; Li, Xuejin

doi:10.1063/5.0139641

Cited by 9 publications

(6 citation statements)

References 82 publications

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“…In such in vitro network structures, which often consist of multiple series-connected bifurcations, the CFL in successive bifurcations is crucially impacted by the RBC distribution in the previous bifurcation. 33,34,72,81,82 Merlo et al 72 recently experimentally demonstrated that upstream bifurcations drive the spatial distribution of healthy RBCs in model microfluidic networks. The authors showed that persistent perturbations in the hematocrit profile after diverging bifurcations affect RBC partitioning at the next bifurcations.…”

Section: Discussionmentioning

confidence: 99%

Cell-free layer development and spatial organization of healthy and rigid red blood cells in a microfluidic bifurcation

et al. 2023

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Section: Discussionmentioning

confidence: 99%

Cell-free layer development and spatial organization of healthy and rigid red blood cells in a microfluidic bifurcation

et al. 2023

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“…DPD is a mesoscopic particle-based simulation technique, where each DPD particle represents an aggregate of molecules interacting with others through soft pairwise forces [36, 37]. This method accurately captures the hydrodynamic behavior of fluids at the mesoscale and has proven successful in investigating complex fluid systems [38, 21, 39, 40]. The evolution of computational capabilities in the past two decades has fostered the advancement and application of multiscale biophysical models for RBCs.…”

Section: Methods and Modelsmentioning

confidence: 99%

“…Consequently, we employ a passive model to replicate the deformation of the spleen sinus during cell traversal through the slit. The configuration in Figure 2A depicts an RBC navigating IES, wherein we employ the worm-like string model for the endothelial cell, a model widely utilized in diverse works [63, 64, 65]. The endothelial cell’s surface is represented by a 2D triangulated network comprising N v vertices (DPD particles).…”

Section: Methods and Modelsmentioning

confidence: 99%

Red blood cell passage through deformable interendothelial slits in the spleen: Insights into splenic filtration and hemodynamics

Li,

Ndou

et al. 2024

Preprint

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The spleen constantly clears altered red blood cells (RBCs) from the circulation, tuning the balance between RBC formation (erythropoiesis) and removal. The retention and elimination of RBCs occur predominantly in the open circulation of the spleen, where RBCs must cross submicron-wide inter-endothelial slits (IES). Several experimental and computational studies have illustrated the role of IES in filtrating the biomechanically and morphologically altered RBCs based on a rigid wall assumption. However, these studies also reported that when the size of IES is close to the lower end of clinically observed sizes (less than 0.5μm), an unphysiologically large pressure difference across the IES is required to drive the passage of normal RBCs, sparking debates on the feasibility of the rigid wall assumption. In this work, we perform a computational investigation based on dissipative particle dynamics (DPD) to explore the impact of the deformability of IES on the filtration function of the spleen. We simulate two deformable IES models, namely the passive model and the active model. In the passive model, we implement the worm-like string model to depict the IES’s deformation as it interacts with blood plasma and allows RBC to traverse. In contrast, the active model involved regulating the IES deformation based on the local pressure surrounding the slit. To demonstrate the validity of the deformable model, we simulate the filtration of RBCs with varied size and stiffness by IES under three scenarios: 1) a single RBC traversing a single slit; 2) a suspension of RBCs traversing an array of slits, mimickingin vitrospleen-on-a-chip experiments; 3) RBC suspension passing through the 3D spleen filtration unit known as ‘the splenon’. Our simulation results of RBC passing through a single slit show that the deformable IES model offers more accurate predictions of the critical cell surface area to volume ratio that dictate the removal of aged RBCs from circulation compared to prior rigid-wall models. Our biophysical models of the spleen-on-a-chip indicates a hierarchy of filtration function stringency: rigid model > passive model > active model, providing a possible explanation of why the spleen-on-a-chip could overestimate the filtration function of IES. We also illustrate that the biophysical model of ‘the splenon’ enables us to replicate theex vivoexperiments involving spleen filtration of malaria-infected RBCs. Taken together, our simulation findings indicate that the deformable IES model could serve as a mesoscopic representation of spleen filtration function closer to physiological reality, addressing questions beyond the scope of current experimental and computational models and enhancing our understanding of the fundamental flow dynamics and mechanical clearance processes within in the human spleen.

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“…DPD method and cellular level blood cell models Several computational models of RBCs have been developed in the last two decades to simulate the dynamics of normal and diseased RBCs. Based on their level of complexity, these RBC models can be categorized into the protein-level RBC models [67][68][69][70][71][72][73][74][75][76][77], which are widely used in simulating the pathological alterations of RBC membrane structure in blood disorders, and cellular-level RBC models [72,[78][79][80][81][82][83][84][85], which are mostly used in modeling blood cell suspensions or blood flow. Due to the high computational cost of the protein-level RBC models, we employ a cellular-level model [86] developed based on dissipative particle dynamics (DPD) [87] to simulate the normal and sickle RBCs as well as macrophages (more details on the cellular-level models and the values of model parameters can be found in S1 Text).…”

Section: Methodsmentioning

confidence: 99%

A combined computational and experimental investigation of the filtration function of splenic macrophages in sickle cell disease

Qiang

et al. 2023

Preprint

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Being the largest lymphatic organ in the body, the spleen also constantly controls the quality of red blood cells (RBCs) in circulation through its two major filtration components, namely interendothelial slits (IES) and red pulp macrophages. In contrast to the extensive studies in understanding the filtration function of IES, there are relatively fewer works on investigating how the splenic macrophages retain the aged and diseased RBCs, i.e., RBCs in sickle cell disease (SCD). Herein, we perform a computational study informed by companion experiments to quantify the dynamics of RBCs captured and retained by the macrophages. We first calibrate the parameters in the computational model based on microfluidic experimental measurements for sickle RBCs under normoxia and hypoxia, as those parameters are not available in the literature. Next, we quantify the impact of a set of key factors that are expected to dictate the RBC retention by the macrophages in the spleen, namely, blood flow conditions, RBC aggregation, hematocrit, RBC morphology, and oxygen levels. Our simulation results show that hypoxic conditions could enhance the adhesion between the sickle RBCs and macrophages. This, in turn, increases the retention of RBCs by as much as five-fold, which could be a possible cause of RBC congestion in the spleen of patients with SCD. Our study on the impact of RBC aggregation illustrates a ’clustering effect’, where multiple RBCs in one aggregate can make contact and adhere to the macrophages, leading to a higher retention rate than that resulting from RBC-macrophage pair interactions. Our simulations of sickle RBCs flowing past macrophages for a range of blood flow velocities indicate that the increased blood velocity could quickly attenuate the function of the red pulp macrophages on detaining aged or diseased RBCs, thereby providing a possible rationale for the slow blood flow in the open circulation of the spleen. Furthermore, we quantify the impact of RBC morphology on their tendency to be retained by the macrophages. We find that the sickle and granular-shaped RBCs are more likely to be filtered by macrophages in the spleen. This finding is consistent with the observation of low percentages of these two forms of sickle RBCs in the blood smear of SCD patients. Taken together, our experimental and simulation results aid in our quantitative understanding of the function of splenic macrophages in retaining the diseased RBCs and provide an opportunity to combine such knowledge with the current knowledge of the interaction between IES and traversing RBCs to apprehend the complete filtration function of the spleen in SCD.

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Temporal-spatial heterogeneity of hematocrit in microvascular networks

Cited by 9 publications

References 82 publications

Cell-free layer development and spatial organization of healthy and rigid red blood cells in a microfluidic bifurcation

Cell-free layer development and spatial organization of healthy and rigid red blood cells in a microfluidic bifurcation

Red blood cell passage through deformable interendothelial slits in the spleen: Insights into splenic filtration and hemodynamics

A combined computational and experimental investigation of the filtration function of splenic macrophages in sickle cell disease

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