血流对内皮细胞表面ATP/ADP浓度的影响：剪切应力和质量传递之间的相互作用
Effect of flow on ATP/ADP concentration at the endothelial cell surface: interplay between shear stress and mass transport
摘要：
核苷酸ATP和ADP调节内皮细胞（EC）生物学的许多方面，包括细胞内钙浓度、粘着斑激活、细胞骨架组织和细胞运动。在体内，EC是不断下流，和EC表面上的ATP/ADP的浓度是由核苷酸的对流和扩散运输以及EC表面上的外核苷酸酶水解的组合效应决定的。此外，实验已经证明，流动诱导ATP从细胞释放。以前的计算模型已经纳入了上述影响，从而描述了EC表面的浓度。然而，目前还不清楚是什么物理过程负责核苷酸调控。虽然一些EC响应流已被证明是直接驱动的剪切应力，其他人似乎也涉及一个不可忽略的贡献的运输。在目前的工作中，我们开发了一个数学模型，并进行数值模拟，以调查的相对贡献的剪切应力和运输的核苷酸浓度在EC表面，细胞密度的影响。由于体外实验在某些情况下使用融合细胞，在其他情况下使用亚融合细胞，因此我们还研究了细胞密度对结果的影响。模拟的结果表明，剪切应力和运输之间的复杂的相互作用，使运输有显着的贡献，在某些剪切应力值，但不是在其他。转运对核苷酸浓度的影响随细胞密度增加而增加。目前的研究结果增强了我们的理解的机制，管理这些分子在EC表面下流的调节。这些发现对下游反应如细胞运动的影响值得进一步研究。
英文摘要：
The nucleotides ATP and ADP regulate many aspects of endothelial cell (EC) biology, including intracellular calcium concentrations, focal adhesion activation, cytoskeletal organization, and cellular motility. In vivo, ECs are constantly under flow, and the concentration of ATP/ADP on the EC surface is determined by the combined effects of nucleotide convective and diffusive transport as well as hydrolysis by ectonucleotidases on the EC surface. In addition, experiments have demonstrated that flow induces ATP release from the cells. Previously computational models have incorporated the above effects and thus described concentration at the EC surface. However, it remains unclear what physical processes are responsible for nucleotide regulation. While some EC responses to flow have been shown to be directly driven by shear stress, others appear to also involve a non-negligible contribution of transport. In the present work, we develop a mathematical model and perform numerical simulations to investigate the relative contributions of shear stress and transport to nucleotide concentration at the EC surface, with the effect of cell density. Because in vitro experiments are performed by using confluent cells in some cases and subconfluent cells in other cases, we also investigate the effect of cell density on the results. The outcomes of the simulations demonstrate a complex interplay between shear stress and transport such that transport has a significant contribution at certain shear stress values but not at others. The effect of transport on nucleotide concentration increases with cell density. The present findings enhance our understanding of the mechanisms that govern the regulation of such molecules at the EC surface under flow. The implications of these findings for downstream responses such as cellular motility merit future investigation.
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