Tubule epithelial cells (TECs) regulate the reabsorption of water and electrolytes; however, the role of mechanical force in driving fluid transport by TECs is unclear. Using a microfluidic platform to mimic fluid transport, Choudhury and colleagues now show that TECs act as mechanobiological fluid pumps, actively generating hydraulic pressure gradients across the epithelium. The trans-epithelial fluidic flux, which occurs in an apical-to-basal direction in normal TECs, declines with increasing hydraulic pressure until a stall pressure is reached. Moreover, the researchers show that TECs change their gene expression profiles and spatial arrangements of ion exchangers in response to changes in pressure.