Trans-epithelial Fluid Pumping Performance of Renal Epithelial Cells and Mechanics of Cystic Expansion

Abstract

Using a novel microfluidic platform to recapitulate fluid transport activity of kidney cells, we report that renal epithelial cells can actively generate hydraulic pressure gradients across the epithelium. The fluidic flux declines with increasing hydraulic pressure until a stall pressure, at which the flux vanishes--in a manner similar to mechanical fluidic pumps. The developed pressure gradient translates to a force of 50-100 nanoNewtons per cell. For normal human kidney cells, the fluidic flux is from apical to basal, and the pressure is higher on the basal side. For human Autosomal Dominant Polycystic Kidney Disease (ADPKD) cells, the fluidic flux is reversed from basal to apical with a higher stall pressure. Molecular studies and proteomic analysis reveal that renal epithelial cells are sensitive to hydraulic pressure gradients, developing different expression profiles and spatial arrangements of ion exchangers and the cytoskeleton in different pressure conditions. These results, together with data from osmotic and pharmacological perturbations of fluidic pumping, implicate mechanical force and hydraulic pressure as important variables during morphological changes in epithelial tubules, and provide further insights into pathophysiological mechanisms underlying the development of high luminal pressure within renal cysts.

Extracellular Hydraulic Resistance Enhances Cell Migration

“…NaK has been shown to generate water fluxes. [ 25,26 ] Upon inhibition of NaK by Ouabain, [ 23,27 ] we observed a reduction in cell speed for both control and high viscosity media. However, the speed reduction in viscous media is more pronounced (Figure 3E; Video S3, Supporting Information), suggesting greater contributions of ion and water fluxes in viscous microenvironments.…”