The microvascular networks in the body of vertebrates consist of the smallest vessels such as arterioles, capillaries, and venules. The flow of RBCs through these networks ensures the gas exchange in as well as the transport of nutrients to the tissues. Any alterations in this blood flow may have severe implications on the health state. Since the vessels in these networks obey dimensions similar to the diameter of RBCs, dynamic effects on the cellular scale play a key role. The steady progression in the numerical modeling of RBCs, even in complex networks, has led to novel findings in the field of hemodynamics, especially concerning the impact and the dynamics of lingering events, when a cell meets a branch of the network. However, these results are yet to be matched by a detailed analysis of the lingering experiments in vivo. To quantify this lingering effect in in vivo experiments, this study analyzes branching vessels in the microvasculature of Syrian golden hamsters via intravital microscopy and the use of an implanted dorsal skinfold chamber. It also presents a detailed analysis of these lingering effects of cells at the apex of bifurcating vessels, affecting the temporal distribution of cell-free areas of blood flow in the branches, even causing a partial blockage in severe cases.
The significant rates of post-operative arterial thrombus formation following the sutured anastomosis (surgical connection) of vessels in microvascular reconstruction has kindled the development of engineered solutions such as the UNILINK coupler. These devices reduce thrombosis rates, which recent numerical studies suggest to be due to decreases in shear strain rate across the anastomosis site when compared to sutured vessels. In this work we develop and analytically solve the first mathematical model for the problem of microvascular anastomosis, leading to the discovery that the rates of thr…
In animals, gas exchange between blood and tissues occurs in narrow vessels, whose diameter is comparable to that of a red blood cell. Red blood cells must deform to squeeze through these narrow vessels, transiently blocking or occluding the vessels they pass through. Although the dynamics of vessel occlusion have been studied extensively, it remains an open question why microvessels need to be so narrow. We study occlusive dynamics within a model microvascular network: the embryonic zebrafish trunk. We show that pressure feedbacks created when red blood cells enter the finest vessels of the t…
Blood flowing through microvascular bifurcations has been an active research topic for many decades, while the partitioning pattern of nanoscale solutes in the blood remains relatively unexplored. Here, we demonstrate a multiscale computational framework for direct numerical simulation of the nanoparticle (NP) partitioning through physiologically-relevant vascular bifurcations in the presence of red blood cells (RBCs). The computational framework is established by embedding a newly-developed particulate suspension inflow/outflow boundary condition into a multiscale blood flow solver. The compu…
There has been a consistent growth in research involving imaging of microvasculature over the past few decades. By 2008, publications mentioning the microcirculation had grown more than 2000 per annum. Many techniques have been demonstrated for measurement of the microcirculation ranging from the earliest invasive techniques to the present high speed, high resolution non-invasive imaging techniques. Understanding the microvasculature is vital in tackling fundamental research questions as well as to understand effects of disease progression on the physiological wellbeing of an individual. We ha…
Across mammalian species, solute exchange takes place in complex microvascular networks. In the human placenta, the primary exchange units are terminal villi that contain disordered networks of fetal capillaries and are surrounded externally by maternal blood. Here we show how the irregular internal structure of a terminal villus determines its exchange capacity for a wide range of solutes. Distilling geometric features into three scalar parameters, obtained from image analysis and computational fluid dynamics, we capture archetypal features of the the structure-function relationship of termin…
Damage to the blood vessel triggers formation of a hemostatic plug, which is meant to prevent bleeding, yet the same phenomenon may result in a total blockade of a blood vessel by a thrombus, causing severe medical conditions. Here, we show that the physical interplay between platelet adhesion and hemodynamics in a microchannel manifests in a critical threshold behavior of a growing thrombus. Depending on the size of injury, two distinct dynamic pathways of thrombosis were found: the formation of a nonocclusive plug, if injury length does not exceed the critical value, and the total occlusion …
Various biological processes such as transport of oxygen and nutrients, thrombus formation, vascular angiogenesis and remodeling are related to cellular/subcellular level biological processes, where mesoscopic simulations resolving detailed cell dynamics provide a key to understanding and identifying the cellular basis of disease. To break this bottleneck and achieve a biologically meaningful timescale, we propose a multiscale parareal algorithm in which a continuum-based solver supervises a mesoscopic simulation in the time-domain. Using an iterative prediction-correction strategy, the parall…
The primary exchange units in the human placenta are terminal villi, in which fetal capillary networks are surrounded by a thin layer of villous tissue, separating fetal from maternal blood. To understand how the complex spatial structure of villi influences their function, we use an image-based theoretical model to study the effect of tissue metabolism on the transport of solutes from maternal blood into the fetal circulation. For solute that is taken up under first-order kinetics, we show that the transition between flow-limited and diffusion-limited transport depends on two new dimensionles…
Structural microvascular alterations and dysfunction serve as key disease indicators of cancer, diabetes, ischemic stroke, neurodegenerative disorders and many other conditions. In vivo visualization of the microvasculature has traditionally been restricted to millimeter scale depths accessible with optical microscopy. Optoacoustic imaging has enabled breaking through the barrier imposed by light diffusion to map functional hemodynamic parameters in deep-seated vessels, but diffraction and dispersion of ultrasound waves in heterogeneous living tissues prevents reaching capillary resolution. He…
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…
The supply of oxygen and nutrients and the disposal of metabolic waste in the organs depend strongly on how blood, especially red blood cells, flow through the microvascular network. Macromolecular plasma proteins such as fibrinogen cause red blood cells to form large aggregates, called rouleaux, which are usually assumed to be disaggregated in the circulation due to the shear forces present in bulk flow. This leads to the assumption that rouleaux formation is only relevant in the venule network and in arterioles at low shear rates or stasis. Thanks to an excellent agreement between combined e…
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…
Vascular adhesion of circulating tumor cells (CTCs) is a key step in cancer spreading. If inflammation is recognized to favor the formation of vascular metastatic niches, little is known about the contribution of blood rheology to CTC deposition. Herein, a microfluidic chip, covered by a confluent monolayer of endothelial cells, is used for analyzing the adhesion and rolling of colorectal (HCT 15) and breast (MDA MB 231) cancer cells under different biophysical conditions. These include the analysis of cell transport in a physiological solution and whole blood; over a healthy and a TNF alpha i…
Brain is one of the most energy demanding organs in mammals, and its total metabolic rate scales with brain volume raised to a power of around 5/6. This value is significantly higher than the more common exponent 3/4 relating whole body resting metabolism with body mass and several other physiological variables in animals and plants. This article investigates the reasons for brain allometric distinction on a level of its microvessels. Based on collected empirical data it is found that regional cerebral blood flow CBF across gray matter scales with cortical volume $V$ as $CBF \sim V^{-1/6}$, br…
Quantifying the Biophysical Properties of Red Blood Cells in Gaucher Disease
Brown University（布朗大学）；Université Paris Saclay（巴黎萨克雷大学）；CNRS UMR 8000（法国国家科学研究中心第8000联合研究单位）；Institut de Chimie Physique（物理化学研究所）；Université Paris Cité（巴黎西岱大学）；INSERM（法国国家健康与医学研究院）；EFS（法国血液服务机构）；BIGR U1134（BIGR第1134联合研究单位）；Team BioTiGR（BioTiGR团队）；Initiatives IdEx Globule Rouge d’Excellence (InIdex GR-Ex)（卓越红细胞倡议（InIdex GR-Ex））；Team PAMS（PAMS团队）
