Trans-epithelial fluid flow and mechanics of epithelial morphogenesis

Active fluid transport across epithelial monolayers is emerging as a major driving force of tissue morphogenesis in a variety of healthy and diseased systems, as well as during embryonic development. Cells use directional transport of ions and osmotic gradients to drive fluid flow across the cell surface, in the process also building up fluid pressure. The basic physics of this process is described by the osmotic engine model, which also underlies actin-independent cell migration. Recently, the trans-epithelial fluid flux and the hydraulic pressure gradient have been explicitly measured for a variety of cellular and tissue model systems across various species. For the kidney, it was shown that tubular epithelial cells behave as active mechanical fluid pumps: the trans-epithelial fluid flux depends on the hydraulic pressure difference across the epithelial layer. When a stall pressure is reached, the fluid flux vanishes. Hydraulic forces generated from active fluid pumping are important in tissue morphogenesis and homeostasis, and could also underlie multiple morphogenic events seen in other developmental contexts. In this review, we highlight findings that examined the role of trans-epithelial fluid flux and hydraulic pressure gradient in driving tissue-scale morphogenesis. We also review organ pathophysiology due to impaired fluid pumping and the loss of hydraulic pressure sensing at the cellular scale. Finally, we draw an analogy between cellular fluidic pumps and a connected network of water pumps in a city. The dynamics of fluid transport in an active and adaptive network is determined globally at the systemic level, and transport in such a network is best when each pump is operating at its optimal efficiency.