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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. Our analysis revealed a heterogeneous ATP distribution in the network, with higher concentrations in the cell-free layer, concentration peaks around bifurcations and heterogeneity among vessels of the same level. These patterns arise from the spatio-temporal organization of RBCs induced by the network geometry. It is further shown that an alteration of hematocrit and flow strength significantly affects ATP level as well as heterogeneity in the network. These findings constitute a first building block to elucidate the intricate nature of ATP patterns in vascular networks and the far reaching consequences for other biochemical signalling, such as calcium, by ECs.

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. On the contrary, stiff enough particles undergo a biased distribution whereby they follow a deterministic partition at bifurcations, due to long memory. This leads to a lateral ballistic drift in the network at small concentration and anomalous superdiffusion at larger concentration, even though the network is ordered. A further increase of concentration enhances particle-particle interactions which shorten the memory effect, turning the particle anomalous diffusion into a classical diffusion. We expect the drifting and diffusive regime transition to be generic for deformable particles.

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. Using boundary integral formulation we performed numerical simulation of a two dimensional vesicle under shear flow for different values of applied shear rates and time scale of bond kinetics. We observe that the vesicle demonstrates three steady state configurations - adhered, pinned and detached for fast enough ligand-receptor kinetics (akin to Lennard-Jones adhesion). However, for slow bond kinetics the pinned state is not observed. We present scaling laws for the critical shear rates corresponding to the transitions among these three states. These results can help with identifying the processes of cell adhesion/detachment in the blood stream, prevalent features during the immune response and cancer metastasis.

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. Here we investigate such a rich behavior via numerical simulations. We focus on the brush hydrodynamic response at low Reynolds numbers, observing a significant fluid flow reduction inside a polymer-brush coated channel. We find that the reduction of the flow inside the channel is significantly larger than what would happen if the brush effect consisted only in reducing the effective channel width. This amplified reduction is understood as being due to the morphological instability of the brush-liquid interface which is shown to have an elastic origin: the mechanical stress acting on the brush due to the imposed flow is partially released by the interface modulation. In turn, this modulation dissipates more energy than a flat interface in the surrounding fluid, causing a reduction of flow velocity. Our results and interpretations provide an explanation for recent experimental measurements.

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. We show here experimental and computational evidence that leukocytes do swim, and that efficient propulsion is not fueled by waves of cell deformation but by a rearward and inhomogeneous treadmilling of the cell external membrane. Our model consists of a molecular paddling by transmembrane proteins linked to and advected by the actin cortex, whereas freely diffusing transmembrane proteins hinder swimming. Furthermore, continuous paddling is enabled by a combination of external treadmilling and selective recycling by internal vesicular transport of cortex-bound transmembrane proteins. This mechanism explains observations that swimming is five times slower than the retrograde flow of cortex and also that lymphocytes are motile in nonadherent confined environments. Resultantly, the ubiquitous ability of mammalian amoeboid cells to migrate in two dimensions or three dimensions and with or without adhesion can be explained for lymphocytes by a single machinery of heterogeneous membrane treadmilling., (Copyright © 2020. Published by Elsevier Inc.)

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. The effects of wall stiffness and channel confinement on the flow dynamics and swimmer motion are studied. The swimmer motion through the flexible channel is substantially decelerated compared to the rigid channel. The strong confinement in the amply flexible channel imprisons the swimmer by severely restricting its forward motion. The swimmer velocity in a stiff channel displays nonmonotonic variation with the confinement while it shows monotonic reduction in a highly flexible channel. The physical rationale behind such distinct velocity behaviour in flexible and rigid channels is illustrated using an instantaneous flow field and flow history displayed by the swimmer. This behavior follows from a subtle interplay between the shape changes exhibited by the swimmer and the wall compliance. This study may aid in understanding the influence of elasticity of the surrounding environment on cell motility in immunological surveillance and invasiveness of cancer cells.

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. When Pe is increased further, the particle meanders at a short scale but its trajectory wraps into a circle at a larger scale. Increasing even further, Pe causes the swimmer to escape momentarily the circular trajectory in favor of chaotic motion, which lasts for a certain time, before regaining a circular trajectory, and so on. The chaotic bursts become more and more frequent as Pe increases, until the trajectory becomes fully chaotic, via the intermittency scenario. The statistics of the trajectory is found to be of the run-and-tumble-like nature at a short enough time and of diffusive nature at a long time without any source of noise.

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 chemo-mechanical 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., (Copyright © 2018 Biophysical Society. Published by Elsevier Inc. All rights reserved.)