PTEN inhibition improves wound healing in lung epithelia through changes in cellular mechanics that enhance migration

Cosmin Mihai, Shengying Bao, Ju Ping Lai, Samir N. Ghadiali, Daren L Knoell

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

The phosphoinositide-3 kinase/Akt pathway is a vital survival axis in lung epithelia. We previously reported that inhibition of phosphatase and tensin homolog deleted on chromosome 10 (PTEN), a major suppressor of this pathway, results in enhanced wound repair following injury. However, the precise cellular and biomechanical mechanisms responsible for increased wound repair during PTEN inhibition are not yet well established. Using primary human lung epithelia and a related lung epithelial cell line, we first determined whether changes in migration or proliferation account for wound closure. Strikingly, we observed that cell migration accounts for the majority of wound recovery following PTEN inhibition in conjunction with activation of the Akt and ERK signaling pathways. We then used fluorescence and atomic force microscopy to investigate how PTEN inhibition alters the cytoskeletal and mechanical properties of the epithelial cell. PTEN inhibition did not significantly alter cytoskeletal structure but did result in large spatial variations in cell stiffness and in particular a decrease in cell stiffness near the wound edge. Biomechanical changes, as well as migration rates, were mediated by both the Akt and ERK pathways. Our results indicate that PTEN inhibition rapidly alters biochemical signaling events that in turn provoke alterations in biomechanical properties that enhance cell migration. Specifically, the reduced stiffness of PTEN-inhibited cells promotes larger deformations, resulting in a more migratory phenotype. We therefore conclude that increased wound closure consequent to PTEN inhibition occurs through enhancement of cell migration that is due to specific changes in the biomechanical properties of the cell.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume302
Issue number3
DOIs
StatePublished - Feb 1 2012

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Mechanics
Wound Healing
Epithelium
Lung
Wounds and Injuries
Cell Movement
MAP Kinase Signaling System
Epithelial Cells
Chromosomes, Human, Pair 10
1-Phosphatidylinositol 4-Kinase
Atomic Force Microscopy
Phosphoric Monoester Hydrolases
Fluorescence
Phenotype
Cell Line
Survival

Keywords

  • Acute lung injury
  • Akt
  • Cell mechanics
  • Epithelium
  • Erk
  • Lung repair
  • Phosphatase and tensin homolog deleted on chromosome 10
  • Wound remodeling

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology
  • Physiology

Cite this

PTEN inhibition improves wound healing in lung epithelia through changes in cellular mechanics that enhance migration. / Mihai, Cosmin; Bao, Shengying; Lai, Ju Ping; Ghadiali, Samir N.; Knoell, Daren L.

In: American Journal of Physiology - Lung Cellular and Molecular Physiology, Vol. 302, No. 3, 01.02.2012.

Research output: Contribution to journalArticle

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