Osmotic Gradients in Epithelial Acini Increase Mechanical Tension across E-cadherin, Drive Morphogenesis, and Maintain Homeostasis.
3D live FRET imaging
CFTR activity
E-cadherin
acini culture
biophysics
epithelial morphogenesis
mechanobiology
osmotic pressure
Journal
Current biology : CB
ISSN: 1879-0445
Titre abrégé: Curr Biol
Pays: England
ID NLM: 9107782
Informations de publication
Date de publication:
24 02 2020
24 02 2020
Historique:
received:
11
03
2019
revised:
04
10
2019
accepted:
09
12
2019
pubmed:
28
1
2020
medline:
14
1
2021
entrez:
28
1
2020
Statut:
ppublish
Résumé
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 of 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.
Identifiants
pubmed: 31983640
pii: S0960-9822(19)31620-3
doi: 10.1016/j.cub.2019.12.025
pmc: PMC7153951
mid: NIHMS1569585
pii:
doi:
Substances chimiques
Cadherins
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
624-633.e4Subventions
Organisme : NIAMS NIH HHS
ID : R03 AR068096
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL133163
Pays : United States
Organisme : NIGMS NIH HHS
ID : R35 GM119617
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA016059
Pays : United States
Organisme : NIBIB NIH HHS
ID : T32 EB003392
Pays : United States
Informations de copyright
Copyright © 2019 Elsevier Ltd. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Interests The authors declare no competing interests.
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