Kidney epithelial cells are active mechano-biological fluid pumps
Mohammad Ikbal Choudhury, Yizeng Li, Panagiotis Mistriotis, Ana Carina Nogueira Vasconcelos, Eryn E. Dixon, Jing Yang, Morgan Benson, Debonil Maity, Rebecca Walker, Leigha Martin, Fatima Koroma, Feng Qian, Κωνσταντίνος Κωνσταντόπουλος, Owen M. Woodward, Sean X. Sun
Abstract
The role of mechanical forces driving kidney epithelial fluid transport and morphogenesis in kidney diseases is unclear. Here, using a 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, in a manner similar to mechanical fluid pumps. 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 cells, the fluidic flux is reversed from basal to apical. Molecular and proteomic studies reveal that renal epithelial cells are sensitive to hydraulic pressure gradients, changing gene expression profiles and spatial arrangements of ion exchangers and the cytoskeleton in different pressure conditions. These results implicate mechanical force and hydraulic pressure as important variables during kidney function and morphological change, and provide insights into pathophysiological mechanisms underlying the development and transduction of hydraulic pressure gradients.