The 2-pore domain potassium channel TREK-1 regulates stretch-induced detachment of alveolar epithelial cells

Esra Roan, Christopher M. Waters, Bin Teng, Manik Ghosh, Andreas Schwingshackl

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

Acute Respiratory Distress Syndrome remains challenging partially because the underlying mechanisms are poorly understood. While inflammation and loss of barrier function are associated with disease progression, our understanding of the biophysical mechanisms associated with ventilator-associated lung injury is incomplete. In this line of thinking, we recently showed that changes in the F-actin content and deformability of AECs lead to cell detachment with mechanical stretch. Elsewhere, we discovered that cytokine secretion and proliferation were regulated in part by the stretch-activated 2-pore domain K+ (K2P) channel TREK-1 in alveolar epithelial cells (AECs). As such, the aim of the current study was to determine whether TREK-1 regulated the mechanobiology of AECs through cytoskeletal remodeling and cell detachment. Using a TREK-1-deficient human AEC line (A549), we examined the cytoskeleton by confocal microscopy and quantified differences in the F-actin content. We used nano-indentation with an atomic force microscope to measure the deformability of cells and detachment assays to quantify the level of injury in our monolayers. We found a decrease in F-actin and an increase in deformability in TREK-1 deficient cells compared to control cells. Although total vinculin and focal adhesion kinase (FAK) levels remained unchanged, focal adhesions appeared to be less prominent and phosphorylation of FAK at the Tyr925 residue was greater in TREK-1 deficient cells. TREK-1 deficient cells have less F-actin and are more deformable making them more resistant to stretch-induced injury.

Original languageEnglish
Article numbere89429
JournalPLoS ONE
Volume9
Issue number2
DOIs
StatePublished - Feb 19 2014

ASJC Scopus subject areas

  • General

Fingerprint

Dive into the research topics of 'The 2-pore domain potassium channel TREK-1 regulates stretch-induced detachment of alveolar epithelial cells'. Together they form a unique fingerprint.

Cite this