Electrical cues regulate hydrostatic pressure and swelling in cysts and organoids*

Lumenization of epithelium is an essential and ubiquitous step across the morphogenic processes needed to produce hollow structures such as alveoli, kidney ducts, and the gut. Once a lumen is established, it undergoes cycles of swelling and relaxation that precede multiple critical developmental events such as branching. Here, we show that electrical cues can drive the swelling of homotypic epithelial cysts and intestinal organoids. This behavior appears to be driven by electrical modulation of key ion channels responsible for chloride ion transport such as CFTR, which we demonstrate through the use of targeted ion channel inhibitors. Interestingly, the level of swelling varies directly with the strength of the electric field, allowing us to program both the rate of growth and the overall size of a spherical cyst or organoid. The rate of swelling is too rapid to implicate cell proliferation, so we hypothesize hyperelastic deformation of the epithelium. To investigate this, we modify a simple energy-minimization model to consider the effect of stimulation on osmotic pressure, hydrostatic pressure, and ion-mediated pumping to predict accelerated cyst swelling.