Regulating transepithelial transport with electric fields

The kidney, intestine, and lung act as electromechanical pumps, as a key function of the epithelial cells that line these organs is to move fluid across them. The hydrostatic pressure resulting from pumping appears also to be important in determining the shape and form of organs. Our previous work has demonstrated that physiological DC electrical stimulation of engineered hollow kidney cell spheroids (cysts) causes rapid pressurization through fluid flux into the cysts by regulating the function of key ion channels on the cell membrane that contribute to osmotic gradients and water flow. Hence, the epithelium is an active ‘pumping’ material whose transport function can be programmed using electric fields! Our key challenge is to characterize the pumping response of engineered kidney tissues to external electrical control. For this purpose, we created a patterned substrate with contiguous swelling and non-swelling regions consisting of hydrogel and PDMS, respectively. MDCK-II kidney cells form a confluent monolayer over the entire substrate, and when we apply DC stimulation, we observe de-swelling in Matrigel-based hydrogels and swelling in collagen hydrogels. These responses suggest a complex relationship between the electromechanical micro-environment and pumping direction. We imagine applications of this concept in kidney tissue-based soft robotic actuators, biomedical devices for renal disease, and engineering complex tissue geometries.