Epithelial cells spontaneously form acini (also known as cysts or spheroids) with
a single, fluid-filled central lumen, when grown in 3D matrices. The size of the lumen
is dependent on apical secretion of chloride ions, most notably by the CFTR channel,
which has been suggested to establish pressure in the lumen due to water influx. To
study the cellular biomechanics of acini morphogenesis and homeostasis we used MDCK-2
cells. Using FRET-force biosensors for E-cadherin we observed significant increases
in the average tension per molecule for each protein in mature 3D acini as compared
to 2D monolayers. Increases in CFTR activity resulted in increased E-cadherin forces,
indicating that ionic gradients affect cellular tension. Direct measurements of pressure
revealed that mature acini experience significant internal hydrostatic pressure (37
+/− 10.9 Pa). Changes in CFTR activity resulted in pressure and/or volume changes,
both which affect E-cadherin tension. Increases in CFTR chloride secretion also induced
YAP signaling and cellular proliferation. In order to recapitulate disruption of acinar
homeostasis, we induced epithelial to mesenchymal transition (EMT). During the initial
stages of EMT there was a gradual decrease in E-cadherin force and lumen pressure
that correlated with lumen infilling. Strikingly, increasing CFTR activity was sufficient
to block EMT. Our results show that ion secretion is an important regulator of morphogenesis
and homeostasis in epithelial acini. Furthermore, this work demonstrates that for
closed 3D cellular systems, ion gradients can generate osmotic pressure or volume
changes, both of which result in increased cellular tension. Narayanan et al. describe
the role of ion secretion in the generation of osmotic pressure and changes in mechanical
tension across E-cadherin in epithelial acini. Increasing the osmotic gradient increased
force exerted across E-cadherin, induced cellular proliferation and also blocked EMT
progression.