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Despite decades of research on blood flow, an analogue of Navier-Stokes equations that accurately describe blood flow properties has not been established yet. The reason behind this is that the properties of blood flow seem \`a priori non universal as they depend on various factors such as global concentration of red blood cells (RBCs) and channel width. Here, we have discovered a universal law when the stress and strain rate are measured at a given local RBCs concentration. However, the local concentration must be determined in order to close the problem. We propose a non-local diffusion equation of RBCs concentration that agrees with the full simulation. The universal law is exemplified for both shear and pressure driven flows. While the theory is restricted to a simplistic geometry (straight channel) it provides a fundamental basis for future research on blood flow dynamics and could lead to the development of a new theory that accurately describes blood flow properties under various conditions, such as in complex vascular networks.

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. For example, in diabetes mellitus glycocalyx of erythrocytes and of endothelial cells is known to be impaired, a potential source of blood occlusion in microcirculation, which may lead to blindness, and renal failure of patients. The impact of glycocalyx impairment on erythrocyte aggregation remains a largely unexplored research area. We conduct here in vitro-experiments in microfluidic devices in order to investigate erythrocytes aggregation incubated with amylase, an enzyme that partially breaks down glycocalyx molecules. It is found that incubation of erythrocytes by amylase leads to a dramatic increase of their aggregation and stability and alters the aggregates morphologies. Confocal microscopy analysis reveals a significant degradation of the glycocalyx layer, correlated with enhanced erythrocytes aggregation. An increased erythrocyte aggregation in vivo should affect oxygen and other metabolites delivery to organs and tissues. This study brings new elements about elucidation of microscopic origins of erythrocyte aggregation and their potential impact on cardiovascular pathologies.

Lift force of viscous origin is widespread across disciplines, from mechanics to biology. Here, we present the first direct measurement of the lift force acting on a particle moving in a viscous fluid along the liquid interface that separates two liquids. The force arises from the coupling between the viscous flow induced by the particle motion and the capillary deformation of the interface. The measurements show that the lift force increases as the distance between the sphere and the interface decreases, reaching saturation at small distances. The experimental results are in good agreement with the model and numerical calculation developed within the framework of the soft lubrication theory.

We develop a numerical a framework to study phoretic particle dynamics in two dimensions. The particles are modeled as chemically active rigid circles, which can emit or absorb a solute into surrounding fluid. The interaction between particles and solute induces a slip flow on particle surfaces, and the solute is advected by the fluid flow and diffuses with a constant diffusivity. The fluid-structure interaction is resolved by a boundary integral method accelerated by Ewald-like decomposition. The sharp resolution of moving boundaries for solute kinetics is performed thanks to an overlapping mesh method. The framework is validated separately for the Stokes problem and the advection--diffusion problem, reaching relatively high order of accuracy. Moreover, we employ the framework to more general problems, including particles in nearly infinite domain and straight channels, and multiparticle motions., Comment: 26 pages, 13 figures

Several nonlinear and nonequilibrium driven as well as active systems (e.g. microswimmers) show bifurcations from one state to another (for example a transition from a non motile to motile state for microswimmers) when some control parameter reaches a critical value. Bifurcation analysis relies either on a regular perturbative expansion close to the critical point, or on a direct numerical simulation. While many systems exhibit a regular bifurcation such as a pitchfork one, other systems undergo a singular bifurcation not falling in the classical nomenclature, in that the bifurcation normal form is not analytic. We present a swimmer model which offers an exact solution showing a singular normal form, and serves as a guide for the general theory. We provide an adequate general regularization theory that allows us to handle properly the limit of singular bifurcations, and provide several explicit examples of normal forms of singular bifurcations. This study fills a longstanding gap in bifurcations theory., Comment: 9 pages 3 figures

Vesicles are soft elastic bodies with distinctive mechanical properties such as bending resistance, membrane fluidity, and their strong ability to deform, mimicking some properties of biological cells. While previous three-dimensional (3D) studies have identified stationary shapes such as slipper and axisymmetric ones, we report a complete phase diagram of 3D vesicle dynamics in a bounded Poiseuille flow with two more oscillatory dynamics, 3D snaking and swirling. 3D snaking is characterized by planar oscillatory motion of the mass center and shape deformations, which is unstable and leads to swirling or slipper. Swirling emerges from supercritical pitchfork bifurcation. The mass center moves along a helix, the preserved shape rolls on itself and spins around the flow direction. Swirling can coexist with slipper., Comment: 6 pages, 6 figures

Red blood cells (RBCs) -- erythrocytes -- suspended in plasma tend to aggregate and form rouleaux. During aggregation the first stage consists in the formation of RBC doublets [Blood cells, molecules, and diseases 25, 339 (1999)]. While aggregates are normally dissociated by moderate flow stresses, under some pathological conditions the aggregation becomes irreversible, which leads to high blood viscosity and vessel occlusion. We perform here two-dimensional simulations to study the doublet dynamics under shear flow in different conditions and its impact on rheology. We sum up our results on the dynamics of doublet in a rich phase diagram in the parameter space (flow strength, adhesion energy) showing four different types of doublet configurations and dynamics. We find that membrane tank-treading plays an important role in doublet disaggregation, in agreement with experiments on RBCs. A remarkable feature found here is that when a single cell performs tumbling (by increasing vesicle internal viscosity) the doublet formed due to adhesion (even very weak) remains stable even under a very strong shear rate. It is seen in this regime that an increase of shear rate induces an adaptation of the doublet conformation allowing the aggregate to resist cell-cell detachment. We show that the normalized effective viscosity of doublet suspension increases significantly with the adhesion energy, a fact which should affect blood perfusion in microcirculation., Comment: 14pages

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 the 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 in vitro the effect of such a reduction in shear stress on shear-adapted endothelial cells. We find that, within one hour of exposition to reduced wall shear stress, human umbilical vein endothelial cells undergo a 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 cells' phenotype due to altered flow.

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. We analytically find super- and subcritical bifurcations from a non-motile to a motile state and also spontaneous polarity oscillations that arise from a Hopf bifurcation. Relaxing the spherical assumption, the obtained shapes show appealing trends.

Flux of rigid or soft particles (such as drops, vesicles, red blood cells, etc.) in a channel is a complex function of particle concentration, which depends on the details of induced dissipation and suspension structure due to hydrodynamic interactions with walls or between neighboring particles. Through two-dimensional and three-dimensional simulations and a simple model that reveals the contribution of the main characteristics of the flowing suspension, we discuss the existence of an optimal volume fraction for cell transport and its dependence on the cell mechanical properties. The example of blood is explored in detail, by adopting the commonly used modeling of red blood cells dynamics. We highlight the complexity of optimization at the level of a network, due to the antagonist evolution of local volume fraction and optimal volume fraction with the channels diameter. In the case of the blood network, the most recent results on the size evolution of vessels along the circulatory network of healthy organs suggest that the red blood cell volume fraction (hematocrit) of healthy subjects is close to optimality, as far as transport only is concerned. However, the hematocrit value of patients suffering from diverse red blood cel pathologies may strongly deviate from optimality., Comment: arXiv admin note: substantial text overlap with arXiv:1802.05353

We present a numerical study of the time-dependent motion of a two-dimensional vesicle in a channel under an imposed flow. In a Poiseuille flow the shape of the vesicle depends on the flow strength, the mechanical properties of the membrane, and the width of the channel as reported in the past. This study is focused on the centered snaking (CSn) shape, where the vesicle shows an oscillatory motion like a swimmer flagella even though the flow is stationary. We quantify this behavior by the amplitude and frequency of the oscillations of the vesicle's center of mass. We observe regions in parameter space, where the CSn coexists with the parachute or the unconfined slipper. The influence of an amplitude modulation of the imposed flow on the dynamics and shape of the snaking vesicle is also investigated. For large modulation amplitudes transitions to static shapes are observed. A smaller modulation amplitude induces a modulation in amplitude and frequency of the center of mass of the snaking vesicle. In a certain parameter range we find that the center of mass oscillates with a constant envelope indicating the presence of at least two stable states., Comment: 10 pages, 7 figures

Optimal hematocrit $H_o$ maximizes oxygen transport. In healthy humans, the average hematocrit $H$ is in the range of 40-45$\%$, but it can significantly change in blood pathologies such as severe anemia (low $H$) and polycythemia (high $H$). Whether the hematocrit level in humans corresponds to the optimal one is a long standing physiological question. Here, using numerical simulations with the Lattice Boltzmann method and two mechanical models of the red blood cell (RBC) we predict the optimal hematocrit, and explore how altering the mechanical properties of RBCs affects $H_o$. We develop a simplified analytical theory that accounts for results obtained from numerical simulations and provides insight into the physical mechanisms determining $H_o$. Our numerical and analytical models can easily be modified to incorporate a wide range of mechanical properties of RBCs as well as other soft particles thereby providing means for the rational design of blood substitutes. Our work lays the foundations for systematic theoretical study of the optimal hematocrit and its link with pathological RBCs associated with various diseases (e.g. sickle cell anemia, diabetes mellitus, malaria, elliptocytosis).

Driven or active suspensions can display fascinating collective behavior, where coherent motions or structures arise on a scale much larger than that of the constituent particles. Here, we report experiments and numerical simulations revealing that red blood cells (RBCs) assemble into regular patterns in a confined shear flow. The order is of pure hydrodynamic and inertialess origin, and emerges from a subtle interplay between (i) hydrodynamic repulsion by the bounding walls which drives deformable cells towards the channel mid-plane and (ii) intercellular hydrodynamic interactions which can be attractive or repulsive depending on cell-cell separation. Various crystal-like structures arise depending on RBC concentration and confinement. Hardened RBCs in experiments and rigid particles in simulations remain disordered under the same conditions where deformable RBCs form regular patterns, highlighting the intimate link between particle deformability and the emergence of order. The difference in structuring ability of healthy (deformable) and diseased (stiff) RBCs creates a flow signature potentially exploitable for diagnosis of blood pathologies.

Plasma proteins such as fibrinogen induce the aggregation of red blood cells (RBC) into rouleaux, which are responsible for the pronounced shear thinning behavior of blood, control the erythro- cyte sedimentation rate (ESR) a common hematological test and are involved in many situations of physiological relevance such as structuration of blood in the microcirculation or clot formation in pathological situations. Confocal microscopy is used to characterize the shape of RBCs within rouleaux at equilibrium as a function of macromolecular concentration, revealing the diversity of contact zone morphology. Three different configurations that have only been partly predicted before are identified, namely parachute, male-female and sigmoid shapes, and quantitatively recovered by numerical simulations. A detailed experimental and theoretical analysis of clusters of two cells shows that the deformation increases nonlinearly with the interaction energy. Models indicate a forward bifurcation in which the contacting membrane undergoes a buckling instability from a flat to a de- formed contact zone at a critical value of the interaction energy. These results are not only relevant for the understanding of the morphology and stability of RBC aggregates, but also for a whole class of interacting soft deformable objects such as vesicles, capsules or cells in tissues., Comment: 22 pages, 12 figures

The mechanism of hydrodynamics-induced pairing of soft particles, namely closed bilayer membranes (vesicles, a model system for red blood cells) and drops, is studied numerically with a special attention paid to the role of the confinement (the particles are within two rigid walls). This study unveils the complexity of the pairing mechanism due to hydrodynamic interactions. We find both for vesicles and for drops that two particles attract each other and form a stable pair at weak confinement if their initial separation is below a certain value. If the initial separation is beyond that distance, the particles repel each other and adopt a longer stable interdistance. This means that for the same confinement we have (at least) two stable branches. To which branch a pair of particles relaxes with time depends only on the initial configuration. An unstable branch is found between these two stable branches. At a critical confinement the stable branch corresponding to the shortest interdistance merges with the unstable branch in the form of a saddle-node bifurcation. At this critical confinement we have a finite jump from a solution corresponding to the continuation of the unbounded case to a solution which is induced by the presence of walls. The results are summarized in a phase diagram, which proves to be of a complex nature. The fact that both vesicles and drops have the same qualitative phase diagram points to the existence of a universal behavior, highlighting the fact that with regard to pairing the details of mechanical properties of the deformable particles are unimportant. This offers an interesting perspective for simple analytical modeling.

We present experiments on RBCs that flow through microcapillaries under physiological conditions. We show that the RBC clusters form as a subtle imbrication between hydrodynamics interaction and adhesion forces because of plasma proteins. Clusters form along the capillaries and macromolecule-induced adhesion contribute to their stability. However, at high yet physiological flow velocities, shear stresses overcome part of the adhesion forces, and cluster stabilization due to hydrodynamics becomes stronger. For the case of pure hydrodynamic interaction, cell-to-cell distances have a pronounced bimodal distribution. Our 2D-numerical simulations on vesicles captures the transition between adhesive and non-adhesive clusters at different flow velocities., Comment: 12 pages, 11 figures

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 ($\phi_0$) partition depends strongly on RBC deformability, as long as $\phi_0 <20$% (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 $\phi_0$, 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., Comment: 16 pages

Polymer brushes are increasingly used to tailor surface physicochemistry for various applications such as wetting, adhesion of biological objects, implantable devices, etc. We perform Dissipative Particle Dynamics simulations to study the behavior of dense polymer brushes under flow in a slit-pore channel. We discover that the system displays flow inversion at the brush interface for several disconnected ranges of the imposed flow. We associate such phenomenon to collective polymer dynamics: a wave propagating on the brush surface. The relation between the wavelength, the amplitude and the propagation speed of the flow-generated wave is consistent with the solution of the Stokes equations when an imposed traveling wave is assumed as boundary condition (the famous Taylor's swimmer)., Comment: 5 pages, 6 figures, supplemental material (5 pages, 4 figures) attached below the letter and before bibliography, videos available on request to the corresponding author, submitted to SciRep

Many processes in eukaryotic cells, including cell motility, rely on the growth of branched actin networks from surfaces. Despite its central role the mechano-chemical coupling mechanisms which guide the growth process are poorly understood, and a general continuum description combining growth and mechanics is lacking. We develop a theory that bridges the gap between mesoscale and continuum limit and propose a general framework providing the evolution law of actin networks growing under stress. This formulation opens an area for the systematic study of actin dynamics in arbitrary geometries. Our framework predicts a morphological instability of actin growth on a rigid sphere, leading to a spontaneous polarization of the network with a mode selection corresponding to a comet, as reported experimentally. We show that the mechanics of the contact between the network and the surface plays a crucial role, in that it determines directly the existence of the instability. We extract scaling laws relating growth dynamics and network properties offering basic perspectives for new experiments on growing actin networks., Comment: 7 pages, 4 figures

The unique ability of a red blood cell to flow through extremely small microcapillaries depends on the viscoelastic properties of its membrane. Here, we study in vitro the response time upon flow startup exhibited by red blood cells confined into microchannels. We show that the characteristic transient time depends on the imposed flow strength, and that such a dependence gives access to both the effective viscosity and the elastic modulus controlling the temporal response of red cells. A simple theoretical analysis of our experimental data, validated by numerical simulations, further allows us to compute an estimate for the two-dimensional membrane viscosity of red blood cells, $\eta_{mem}^{2D}\sim 10^{-7}$ N$\cdot$s$\cdot$m$^{-1}$. By comparing our results with those from previous studies, we discuss and clarify the origin of the discrepancies found in the literature regarding the determination of $\eta_{mem}^{2D}$, and reconcile seemingly conflicting conclusions from previous works.

Red blood cells (RBCs) are the major component of blood and the flow of blood is dictated by that of RBCs. We employ vesicles, which consist of closed bilayer membranes enclosing a fluid, as a model system to study the behavior of RBCs under a confined Poiseuille flow. We extensively explore two main parameters: i) the degree of confinement of vesicles within the channel, and ii) the flow strength. Rich and complex dynamics for vesicles are revealed ranging from steady-state shapes (in the form of parachute and slipper) to chaotic dynamics of shape. Chaos occurs through a cascade of multiple periodic oscillations of the vesicle shape. We summarize our results in a phase diagram in the parameter plane (degree of confinement, flow strength). This finding highlights the level of complexity of a flowing vesicle in the small Reynolds number where the flow is laminar in the absence of vesicles and can be rendered turbulent due to elasticity of vesicles., Comment: acceptd for Phys. Rev. E

The hydrodynamic interaction of two deformable vesicles in shear flow induces a net displacement, in most cases an increase of their distance in the transverse direction. The statistical average of these interactions leads to shear-induced diffusion in the suspension, both at the level of individual particles which experience a random walk made of successive interactions, and at the level of suspension where a non-linear down-gradient diffusion takes place, an important ingredient in the structuring of suspension flows. We make an experimental and computational study of the interaction of a pair of lipid vesicles in shear flow by varying physical parameters, and investigate the decay of the net lateral displacement with the distance between the streamlines on which the vesicles are initially located. This decay and its dependency upon vesicle properties can be accounted for by a simple model based on the well established law for the lateral drift of a vesicle in the vicinity of a wall. In the semi-dilute regime, a determination of self-diffusion coefficients is presented.

Universality has been a key concept for the classification of equilibrium critical phenomena, allowing associations among different physical processes and models. When dealing with non-equilibrium problems, however, the distinction in universality classes is not as clear and few are the examples, as phase separation and kinetic roughening, for which universality has allowed to classify results in a general spirit. Here we focus on an out-of-equilibrium case, unstable crystal growth, lying in between phase ordering and pattern formation. We consider a well established 2+1 dimensional family of continuum nonlinear equations for the local height $h(\mathbf{x},t)$ of a crystal surface having the general form ${\partial_t h(\mathbf{x},t)} = -\mathbf{\nabla}\cdot {[\mathbf{j}(\nabla h) + \mathbf{\nabla}(\nabla^2 h)]}$: $\mathbf{j}(\nabla h)$ is an arbitrary function, which is linear for small $\nabla h$, and whose structure expresses instabilities which lead to the formation of pyramid-like structures of planar size $L$ and height $H$. Our task is the choice and calculation of the quantities that can operate as critical exponents, together with the discussion of what is relevant or not to the definition of our universality class. These aims are achieved by means of a perturbative, multiscale analysis of our model, leading to phase diffusion equations whose diffusion coefficients encapsulate all relevant informations on dynamics. We identify two critical exponents: i) the coarsening exponent, $n$, controlling the increase in time of the typical size of the pattern, $L\sim t^n$; ii) the exponent $\beta$, controlling the increase in time of the typical slope of the pattern, $M \sim t^{\beta}$ where $M\approx H/L$. Our study reveals that there are only two different universality classes..., Comment: 15 pages, new section (VII.A) added, further considerations at the end of section VI

The foundation of continuum elasticity theory is based on two general principles: (i) the force felt by a small volume element from its surrounding acts only through its surface (the Cauchy principle, justified by the fact that interactions are of short range and are therefore localized at the boundary); (ii) the stress tensor must be symmetric in order to prevent spontaneous rotation of the material points. These two requirements are presented to be necessary in classical textbooks on elasticity theory. By using only basic spatial symmetries it is shown that elastodynamics equations can be derived, for high symmetry crystals (the typical case considered in most textbooks), without evoking any of the two above physical principles., Comment: 6 pages

Many nonlinear partial differential equations (PDEs) display a coarsening dynamics, i.e., an emerging pattern whose typical length scale $L$ increases with time. The so-called coarsening exponent $n$ characterizes the time dependence of the scale of the pattern, $L(t)\approx t^n$, and coarsening dynamics can be described by a diffusion equation for the phase of the pattern. By means of a multiscale analysis we are able to find the analytical expression of such diffusion equations. Here, we propose a recipe to implement numerically the determination of $D(\lambda)$, the phase diffusion coefficient, as a function of the wavelength $\lambda$ of the base steady state $u_0(x)$. $D$ carries all information about coarsening dynamics and, through the relation $|D(L)| \simeq L^2 /t$, it allows us to determine the coarsening exponent. The main conceptual message is that the coarsening exponent is determined without solving a time-dependent equation, but only by inspecting the periodic steady-state solutions. This provides a much faster strategy than a forward time-dependent calculation. We discuss our method for several different PDEs, both conserved and not conserved.

We study the step bunching process in three different 1D step flow models and obtain scaling relations for the step bunches formed in the long times limit. The first one was introduced by S.Stoyanov [Jap. J.Appl. Phys. 29, (1990) L659] as the simplest 'realistic' model of step bunching due to drift of the adatoms. Here we show that it could lead to (at least) two different types of step bunching, depending on the magnitude of the drift. The other two models are minimal models: the equations for step velocity are constructed ad hoc from two terms with opposite effects - destabilizing and, respectively, stabilizing the regular step train., Comment: 5 printed pages, 6 (11) figures, published in full text after reviewing process in the book of the Conference Nanoscience and Nanotechnology, Sofia, 2005