7
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: not found
      • Article: not found

      Osmotic Gradients in Epithelial Acini Increase Mechanical Tension across E-cadherin, Drive Morphogenesis, and Maintain Homeostasis

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          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.

          Related collections

          Author and article information

          Journal
          Current Biology
          Current Biology
          Elsevier BV
          09609822
          January 2020
          January 2020
          Article
          10.1016/j.cub.2019.12.025
          7153951
          31983640
          40682c19-dc26-4ebc-8de9-6e8e8fdf9f4d
          © 2020

          https://www.elsevier.com/tdm/userlicense/1.0/

          History

          Comments

          Comment on this article