Cell-Driven Fluid Dynamics: A Physical Model of Active Systemic Circulation.

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.