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 experimental and numerical approaches, we show that despite the large shear rates present in microcapillaries, the presence of either fibrinogen or the synthetic polymer dextran leads to an enhanced formation of robust clusters of red blood cells, even at haematocrits as low as 1%. Robust aggregates are shown to exist in microcapillaries even for fibrinogen concentrations within the healthy physiological range. These persistent aggregates should strongly affect cell distribution and blood perfusion in the microvasculature, with putative implications for blood disorders even within apparently asymptomatic subjects.

Many eukaryotic cells undergo frequent shape changes (described as amoeboid motion) that enable them to move forward. We investigate the effect of confinement on a minimal model of amoeboid swimmer. A complex picture emerges: (i) The swimmer's nature (i.e., either pusher or puller) can be modified by confinement, thus suggesting that this is not an intrinsic property of the swimmer. This swimming nature transition stems from intricate internal degrees of freedom of membrane deformation. (ii) The swimming speed might increase with increasing confinement before decreasing again for stronger confinements. (iii) A straight amoeoboid swimmer's trajectory in the channel can become unstable, and ample lateral excursions of the swimmer prevail. This happens for both pusher- and puller-type swimmers. For weak confinement, these excursions are symmetric, while they become asymmetric at stronger confinement, whereby the swimmer is located closer to one of the two walls. In this study, we combine numerical and theoretical analyses.

Vesicles, closed membranes made of a bilayer of phospholipids, are considered as a biomimetic system for the mechanics of red blood cells. The understanding of their dynamics under flow and their rheology is expected to help the understanding of the behavior of blood flow. We conduct numerical simulations of a suspension of vesicles in two dimensions at a finite concentration in a shear flow imposed by countertranslating rigid bounding walls by using an appropriate Green's function. We study the dynamics of vesicles, their spatial configurations, and their rheology, namely, the effective viscosity η(eff). A key parameter is the viscosity contrast λ (the ratio between the viscosity of the encapsulated fluid over that of the suspending fluid). For small enough λ, vesicles are known to exhibit tank treading (TT), while at higher λ they exhibit tumbling (TB). We find that η(eff) decreases in the TT regime, passes a minimum at a critical λ=λ(c), and increases in the TB regime. This result confirms previous theoretical and numerical works performed in the extremely dilute regime, pointing to the robustness of the picture even in the presence of hydrodynamic interactions. Our results agree also with very recent numerical simulations performed in three dimensions both in the dilute and more concentrated regime. This points to the fact that dimensionality does not alter the qualitative features of η(eff). However, they disagree with recent simulations in two dimensions. We provide arguments about the possible sources of this disagreement.

Red blood cells play a major role in body metabolism by supplying oxygen from the microvasculature to different organs and tissues. Understanding blood flow properties in microcirculation is an essential step towards elucidating fundamental and practical issues. Numerical simulations of a blood model under a confined linear shear flow reveal that confinement markedly modifies the properties of blood flow. A nontrivial spatiotemporal organization of blood elements is shown to trigger hitherto unrevealed flow properties regarding the viscosity η, namely ample oscillations of its normalized value ½η ¼ ðη − η 0 Þ=ðη 0 ϕÞ as a function of hematocrit ϕ (η 0 ¼ solvent viscosity). A scaling law for the viscosity as a function of hematocrit and confinement is proposed. This finding can contribute to the conception of new strategies to efficiently detect blood disorders, via in vitro diagnosis based on confined blood rheology. It also constitutes a contribution for a fundamental understanding of rheology of confined complex fluids. Introduction.-Blood flow in microcirculation is essential for delivery of nutrients and removal of metabolic waste products to or from tissues. These functions are ensured by proper regulation of blood flow down to the capillary level. One of the main factors controlling capillary circulation is microvascular resistance to blood flow. This effect, in spite of extensive investigation, is still to be fully elucidated, and some fundamental issues remain open. Blood is to good approximation a suspension of red blood cells (RBCs). Blood rheology is dictated by dynamics of RBCs and their interaction with blood vessel walls. A significant research effort has been devoted so far to macroscopic rheology [1,2]. Most of the research on rheology in confined geometries has focused on the famous Fahraeus-Lindqvist (FL) effect [3][4][5] (see recent review [6]), where confinement has been shown to strongly affect the rheology, with a decrease in apparent viscosity as the diameter of a vessel decreases. These advances have not exhausted yet the intricate behavior inherent to rheology of confined blood, as reported in this Letter.A property that is commonly of interest for nonconfined suspensions is the viscosity as a function of the volume fraction ϕ, ηðϕÞ. In the dilute regime, i.e., when hydrodynamic interactions between suspended entities can be neglected, η takes the generic form η ¼ η 0 ð1 þ a 1 ϕÞ, where η 0 is the viscosity of the suspending fluid and a 1 is a quantity (the so-called intrinsic viscosity), that depends, in general, on the properties of the suspension. For example, for rigid particles, a 1 is just a universal number and is equal to 5=2; this is the famous Einstein result [7,8]. a 1 was calculated by Taylor [9] for emulsions, and extended to vesicle suspensions (a blood model) quite recently [10]. When the volume fraction increases, hydrodynamic interactions among suspended

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.

Several micro-organisms, such as bacteria, algae, or spermatozoa, use flagellar or ciliary activity to swim in a fluid, while many other micro-organisms instead use ample shape deformation, described as amoeboid, to propel themselves by either crawling on a substrate or swimming. Many eukaryotic cells were believed to require an underlying substratum to migrate (crawl) by using membrane deformation (like blebbing or generation of lamellipodia) but there is now increasing evidence that a large variety of cells (including those of the immune system) can migrate without the assistance of focal adhesion, allowing them to swim as efficiently as they can crawl. This paper details the analysis of amoeboid swimming in a confined fluid by modeling the swimmer as an inextensible membrane deploying local active forces (with zero total force and torque). The swimmer displays a rich behavior: it may settle into a straight trajectory in the channel or navigate from one wall to the other depending on its confinement. The nature of the swimmer is also found to be affected by confinement: the swimmer can behave, on the average over one swimming cycle, as a pusher at low confinement, and becomes a puller at higher confinement, or vice versa. The swimmer's nature is thus not an intrinsic property. The scaling of the swimmer velocity V with the force amplitude A is analyzed in detail showing that at small enough A, V ∼ A 2 /η 2 (where η is the viscosity of the ambient fluid), whereas at large enough A, V is independent of the force and is determined solely by the stroke cycle frequency and swimmer size. This finding starkly contrasts with currently known results found from swimming models where motion is based on ciliary and flagellar activity, where V ∼ A/η. To conclude, two definitions of efficiency as put forward in the literature are analyzed with distinct outcomes. We find that one type of efficiency has an optimum as a function of confinement while the other does not. Future perspectives are outlined.

The steady-state properties of an interface in a stationary Couette flow are addressed within the framework of fluctuating hydrodynamics. Our study reveals that thermal fluctuations are driven out of equilibrium by an effective shear rate that differs from the applied one. In agreement with experiments, we find that the mean-square displacement of the interface is reduced by the flow. We also show that nonequilibrium fluctuations present a certain degree of universality in the sense that all features of the fluids can be factorized into a single control parameter. Finally, the results are discussed in the light of recent experimental and numerical studies.

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