Nitric oxide modelling and its bioavailability influenced by red blood cells.

Nitric oxide (NO) is an important vasodilator responsible for maintaining vascular tone in the human body. Its production in endothelial cells (ECs) is regulated by the rise of cytoplasmic Ca concentration and shear stress perceived by blood flow. The increase in cytoplasmic Ca concentration is mainly activated by adenosine triphosphate (ATP) released from red blood cells (RBCs) and ECs.

Glycocalyx cleavage boosts erythrocytes aggregation.

The glycocalyx is a complex layer of carbohydrate and protein molecules that surrounds the cell membrane of many types of mammalian cells. It serves several important functions, including cell adhesion and communication, and maintain cell shape and stability, especially in the case of erythrocytes. Alteration of glycocalyx composition represents a cardiovascular health threatening.

Reply to the 'Comment on "Dynamics and rheology of vesicles under confined Poiseuille flow"' by G. Coupier and T. Podgorski, , 2024, , DOI: 10.1039/D3SM01679J.

In this answer, we provide our arguments in support of the possibility to observe the single file-organization of red blood cells in microvessels and the resulting unexpectedly weak increase of blood viscosity with increasing hematocrit, the physiological relevance of which was questioned in the comment. The key element is that the equivalent diameter in 3D for the maximal hematocrit corresponding to a single file of red blood cells is about 10 µm and not 20 µm, as in 2D. In addition, the viscosity contrast (ratio between the cell internal and external viscosities) value must be chosen in our 2D simulation in a such a way that the effective viscosity (a linear combination of the internal, external and membrane viscosities) be close to that of a real RBC.

Motility and swimming: universal description and generic trajectories.

Autonomous locomotion is a ubiquitous phenomenon in biology and in physics of active systems at microscopic scale. This includes prokaryotic, eukaryotic cells (crawling and swimming) and artificial swimmers. An outstanding feature is the ability of these entities to follow complex trajectories, ranging from straight, curved (circular, helical.

Dynamics and rheology of vesicles under confined Poiseuille flow.

The rheological behavior and dynamics of a vesicle suspension, serving as a simplified model for red blood cells, are explored within a Poiseuille flow under the Stokes limit. Investigating vesicle response has led to the identification of novel solutions that complement previously documented forms like the parachute and slipper shapes. This study has brought to light the existence of alternative configurations, including a fully off-centered form and a multilobe structure.

Heterogeneous ATP patterns in microvascular networks.

ATP is not only an energy carrier but also serves as an important signalling molecule in many physiological processes. Abnormal ATP level in blood vessel is known to be related to several pathologies, such as inflammation, hypoxia and atherosclerosis. Using advanced numerical methods, we analysed ATP released by red blood cells (RBCs) and its degradation by endothelial cells (ECs) in a cat mesentery-inspired vascular network, accounting for RBC mutual interaction and interactions with vascular walls.

Anomalous Diffusion of Deformable Particles in a Honeycomb Network.

Transport of deformable particles in a honeycomb network is studied numerically. It is shown that the particle deformability has a strong impact on their distribution in the network. For sufficiently soft particles, we observe a short memory behavior from one bifurcation to the next, and the overall behavior consists in a random partition of particles, exhibiting a diffusionlike transport.

Mathematical modeling of intracellular calcium in presence of receptor: a homeostatic model for endothelial cell.

Calcium is a ubiquitous molecule and second messenger that regulates many cellular functions ranging from exocytosis to cell proliferation at different time scales. In the vasculature, a constant adenosine triphosphate (ATP) concentration is maintained because of ATP released by red blood cells (RBCs). These ATP molecules continuously react with purinergic receptors on the surface of endothelial cells (ECs).

Human endothelial cells in high glucose: New clues from culture in 3D microfluidic chips.

Several studies have demonstrated the role of high glucose in promoting endothelial dysfunction utilizing traditional two-dimensional (2D) culture systems, which, however, do not replicate the complex organization of the endothelium within a vessel constantly exposed to flow. Here we describe the response to high glucose of micro- and macro-vascular human endothelial cells (EC) cultured in biomimetic microchannels fabricated through soft lithography and perfused to generate shear stress. In 3D macrovascular EC exposed to a shear stress of 0.

Flow driven vesicle unbinding under mechanosensitive adhesion.

Ligand receptor based adhesion is the primary mode of interaction of cellular blood constituents with the endothelium. These adhered entities also experience shear flow imposed by the blood which may lead to their detachment due to the viscous lift forces. Here, we have studied the role of the ligand-receptor bond kinetics in the detachment of an adhered vesicle (a simplified cell model) under shear flow.

Hydrodynamic instability and flow reduction in polymer brush coated channels.

A polymer brush is a passive medium. At equilibrium the knowledge of its chemical composition and thickness is enough for a full system characterization. However, when the brush is exposed to fluid flow it reveals a much more intriguing nature, in which filamentous protrusions and the way they interact among themselves and with the surrounding fluid are of outmost importance.

Red blood cells under flow show maximal ATP release for specific hematocrit.

ATP release by red blood cells (RBCs) under shear stress (SS) plays a pivotal role in endothelial biochemical signaling cascades. The aim of this study is to investigate through numerical simulation how RBC spatiotemporal organization depends on flow and geometrical conditions to generate ATP patterns. Numerical simulations were conducted in a straight channel by considering both plasma and explicit presence of RBCs, their shape deformation and cell-cell interaction, and ATP release by RBCs.

Amoeboid Swimming Is Propelled by Molecular Paddling in Lymphocytes.

Mammalian cells developed two main migration modes. The slow mesenchymatous mode, like crawling of fibroblasts, relies on maturation of adhesion complexes and actin fiber traction, whereas the fast amoeboid mode, observed exclusively for leukocytes and cancer cells, is characterized by weak adhesion, highly dynamic cell shapes, and ubiquitous motility on two-dimensional and in three-dimensional solid matrix. In both cases, interactions with the substrate by adhesion or friction are widely accepted as a prerequisite for mammalian cell motility, which precludes swimming.

The effect of shear stress reduction on endothelial cells: A microfluidic study of the actin cytoskeleton.

Reduced blood flow, as occurring in ischemia or resulting from exposure to microgravity such as encountered in space flights, induces a decrease in the level of shear stress sensed by endothelial cells forming the inner part of blood vessels. In the present study, we use a microvasculature-on-a-chip device in order to investigate the effect of such a reduction in shear stress on shear-adapted endothelial cells. We find that, within 1 h of exposition to reduced wall shear stress, human umbilical vein endothelial cells undergo reorganization of their actin skeleton with a decrease in the number of stress fibers and actin being recruited into the cells' peripheral band, indicating a fairly fast change in the cells' phenotype due to altered flow.

Amoeboid swimming in a compliant channel.

Several prokaryotes and eukaryotic cells swim in the presence of deformable and rigid surfaces that form confinement. The most commonly observed examples from biological systems are motility of leukocytes and pathogens present within the blood suspension through a microvascular network, and locomotion of eukaryotic cells such as immune system cells and cancerous cells through interstices between soft interstitial cells and the extracellular matrix within the interstitial tissue. This motivated us to investigate numerically the flow dynamics of amoeboid swimming in a flexible channel.

Chaotic Swimming of Phoretic Particles.

The swimming of a rigid phoretic particle in an isotropic fluid is studied numerically as a function of the dimensionless solute emission rate (or Péclet number Pe). The particle sets into motion at a critical Pe. Whereas the particle trajectory is straight at a small enough Pe, it is found that it loses its stability at a critical Pe in favor of a meandering motion.

Crawling in a Fluid.

There is increasing evidence that mammalian cells not only crawl on substrates but can also swim in fluids. To elucidate the mechanisms of the onset of motility of cells in suspension, a model which couples actin and myosin kinetics to fluid flow is proposed and solved for a spherical shape. The swimming speed is extracted in terms of key parameters.

Paroxysmal Permeability Disorders: Development of a Microfluidic Device to Assess Endothelial Barrier Function.

Paroxysmal Permeability Disorders (PPDs) are pathological conditions caused by periodic short lasting increase of endothelial permeability, in the absence of inflammatory, degenerative, ischemic vascular injury. PPDs include primary angioedema, idiopathic systemic capillary leak syndrome and some rare forms of localized retroperitoneal-mediastinal edema. to validate a microfluidic device to study endothelial permeability in flow conditions.

Emerging Attractor in Wavy Poiseuille Flows Triggers Sorting of Biological Cells.

Microflows constitute an important instrument to control particle dynamics. A prominent example is the sorting of biological cells, which relies on the ability of deformable cells to move transversely to flow lines. A classic result is that soft microparticles migrate in flows through straight microchannels to an attractor at their center.

Shear stress in the microvasculature: influence of red blood cell morphology and endothelial wall undulation.

The effect of red blood cells and the undulation of the endothelium on the shear stress in the microvasculature is studied numerically using the lattice Boltzmann-immersed boundary method. The results demonstrate a significant effect of both the undulation of the endothelium and red blood cells on wall shear stress. Our results also reveal that morphological alterations of red blood cells, as occur in certain pathologies, can significantly affect the values of wall shear stress.

Multi-wavelength photo-acoustic microscopy in the frequency domain for simultaneous excitation and detection of dyes.

An optical-resolution photoacoustic microscope with modulated CW laser diodes allowing multi-channel imaging is presented that can be used for both imaging biological tissues and for targeted photo-dynamic therapy (PDT) varying the optical power and exposure time. The effects of this therapy are immediately monitored in order to optimize the time of irradiation. After the description of the experimental setup, and applications are presented on a synthetic sample and on the mouse ear using hemoglobin as endogenous and methylene blue as exogenous dye for imaging and PDT, respectively.

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

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.

Effect of Cytoskeleton Elasticity on Amoeboid Swimming.

Recently, it has been reported that the cells of the immune system, as well as Dictyostelium amoebae, can swim in a bulk fluid by changing their shape repeatedly. We refer to this motion as amoeboid swimming. Here, we explore how the propulsion and the deformation of the cell emerge as an interplay between the active forces that the cell employs to activate the shape changes and the passive, viscoelastic response of the cell membrane, the cytoskeleton, and the surrounding environment.