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. Two ATP release pathways through cell membrane are taken into account: pannexin 1 channel, sensitive to SS, and cystic fibrosis transmembrane conductance regulator, which responds to cell deformation. Several flow and hematocrit conditions are explored. The problem is solved by the lattice Boltzmann method. Application of SS to the RBC suspension triggers a nontrivial spatial RBC organization and ATP patterns. ATP localizes preferentially in the vicinity of the cell-free layer close to channel wall. Conditions for maximal ATP release per cell are identified, which depend on vessel size and hematocrit Ht. Increasing further Ht beyond optimum enhances the total ATP release but should degrade oxygen transport capacity, a compromise between an efficient ATP release and minimal blood dissipation. Moreover, ATP is boosted in capillaries, suggesting a vasomotor activity coordination throughout the resistance network.