Wu Yufei, Benson Morgan A, Sun Sean X
Department of Mechanical Engineering, Johns Hopkins University, Baltimore, Maryland, USA.
Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, Maryland, USA.
bioRxiv. 2024 May 21:2024.05.19.594862. doi: 10.1101/2024.05.19.594862.
Active fluid circulation and transport are key functions of living organisms, which drive efficient delivery of oxygen and nutrients to various physiological compartments. Because fluid circulation occurs in a network, the systemic flux and pressure are not simple outcomes of any given component. Rather, they are emergent properties of network elements and network topology. Moreover, consistent pressure and osmolarity gradients across compartments such as the kidney, interstitium, and vessels are known. How these gradients and network properties are established and maintained is an unanswered question in systems physiology. Previous studies have shown that epithelial cells are fluid pumps that actively generate pressure and osmolarity gradients. Polarization and activity of ion exchangers that drive fluid flux in epithelial cells are affected by pressure and osmolarity gradients. Therefore, there is an unexplored coupling between the pressure and osmolarity in the circulating network. Here we develop a mathematical theory that integrates the influence of pressure and osmolarity on solute transport and explores both cell fluid transport and systemic circulation. This model naturally generates pressure and osmolarity gradients across physiological compartments, and demonstrates how systemic transport properties can depend on cell properties, and how the cell state can depend on systemic properties. When epithelial and endothelial pumps are considered together, we predict how pressures at various points in the network depend on the overall osmolarity of the system. The model can be improved by including physiological geometries and expanding solute species, and highlights the interplay of fluid properties with cell function in living organisms.
活跃的流体循环和运输是生物体的关键功能，它们推动氧气和营养物质有效地输送到各个生理腔室。由于流体循环发生在一个网络中，全身通量和压力并非任何给定组件的简单结果。相反，它们是网络元件和网络拓扑结构的涌现特性。此外，已知跨肾脏、间质和血管等腔室存在一致的压力和渗透压梯度。这些梯度和网络特性是如何建立和维持的，是系统生理学中一个尚未解决的问题。先前的研究表明，上皮细胞是主动产生压力和渗透压梯度的流体泵。驱动上皮细胞中流体通量的离子交换器的极化和活性受压力和渗透压梯度的影响。因此，循环网络中的压力和渗透压之间存在未被探索的耦合关系。在这里，我们开发了一种数学理论，该理论整合了压力和渗透压对溶质运输的影响，并探索了细胞流体运输和全身循环。该模型自然地在生理腔室之间产生压力和渗透压梯度，并展示了全身运输特性如何依赖于细胞特性，以及细胞状态如何依赖于全身特性。当同时考虑上皮泵和内皮泵时，我们预测网络中各个点的压力如何取决于系统的整体渗透压。该模型可以通过纳入生理几何形状和扩展溶质种类来改进，并突出了流体特性与生物体中细胞功能之间的相互作用。
