Pump it up: bioelectric stimulation controls tissue hydrostatic pressure and water transport via electro-inflation

Abstract

Epithelial tissues sheath many organs, separating ‘outside’ from ‘inside’ and exquisitely regulating ion and water transport via electromechanical pumping to maintain homeostatic balance and tissue hydrostatic pressure. While it is becoming increasingly clear that the ionic microenvironment and external electric stimuli can affect epithelial function and behavior, the coupling between electrical perturbation and tissue form remain unclear. We investigated this by combining electrical stimulation with three-dimensional epithelial tissues with hollow ‘lumens’—both kidney cysts and complex intestinal stem cell organoids. Our core finding is that physiological strength electrical stimulation of order 1-3 V/cm (with both direct and alternating currents) can drive powerful and rapid inflation of hollow tissues through a process we call ‘electro-inflation’, inducing a nearly threefold increase in tissue volume and striking asymmetries in tissue form. Electro-inflation is primarily driven by activation of the CFTR ion channel pumping chloride into the tissue, causing water to osmotically flow. This influx generates hydrostatic pressure, and inflation results from a competition between this pressure and cell cytoskeletal tension. We validated these interpretations with computational models connecting ion dynamics in the Diffuse Double Layer around tissues to tissue mechanics. Electro-inflation is a unique biophysical process to study and control complex tissue function.