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

Abstract

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 chemomechanical 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.Under shear flow, both vesicles (in two and three dimensions) and RBCs exhibit the following two main modes: TT (the cell or vesicle acquires a given orientation while the membrane rotates around the center of mass) and TB (a quasi-solid-like flipping). For vesicles, TB occurs at high enough internal fluid viscosity with respect to the external one, whereas TT prevails at low enough internal viscosity (17). For RBCs (18-21), the transition from TB to TT can be achieved by increasing shear stress. For low shear stress, RBCs exhibit TB, whereas for large shear stress, we have TT. Experiments Modeling ATP Release by RBCs under Flow

Rheology of a confined vesicle suspension

“…A prominent example is blood flow where red blood cells (RBCs) interaction with the vessel walls leads to a cell-free layer close to the wall. This cell-free layer plays a pivotal role in oxygen transport, since it leads to a drastic reduction of the effective viscosity with decreasing vessel diameter, allowing thus for a more efficient transport in small vessels of the vascular network where oxygen (and other elements, such as ATP [18]) is delivered to tissues and organs. The decrease of blood viscosity with vessel diameter is known as the Fåhraeus-Lindqvist effect [19].…”

The Relationship between Erythrocytes and Diabetes Mellitus

“…As the product of glycolysis, ATP is the essential energy substance for a variety of biochemical reactions in erythrocytes and maintains the normal function of erythrocytes, such as transmembrane 5 Journal of Diabetes Research ion and lipids exchange and erythrocyte deformation [63]. The glucose uptake rate, enzyme activity, and production and utilization of intermediate metabolites and ATP in the erythrocytes of patients with diabetic were all altered [64][65][66][67][68][69]. The enhancement of the glucose metabolism in erythrocytes of diabetic patients helps in the consumption of excess blood glucose and reduces the formation of glycosylated end-products; on the other hand, it can also increase NADPH production via the pentose phosphate pathway to reduce OS in erythrocytes [70].…”

Primary cilium: a paradigm for integrating mathematical modeling with experiments and numerical simulations in mechanobiology

“…Besides, mechanosensation pathways in simpler red blood cells have also been investigated. For example, Zhang et al applied a Lattice-Boltzmann model to predict the release of ATP due to mechanosensing of red blood cell and the concentration of ATP in the 3D space and how it evolves with time by solving the convection-diffusion-reaction PDEs [ 125 ].…”