E-cadherin-mediated force transduction signals regulate global cell mechanics

Ismaeel Muhamed, Jun Wu, Poonam Sehgal, Xinyu Kong, Arash Tajik, Ning Wang, Deborah E Leckband

Research output: Contribution to journalArticle

Abstract

This report elucidates an E-cadherin-based force-transduction pathway that triggers changes in cell mechanics through a mechanism requiring epidermal growth factor receptor (EGFR), phosphoinositide 3-kinase (PI3K), and the downstream formation of new integrin adhesions. This mechanism operates in addition to local cytoskeletal remodeling triggered by conformational changes in the E-cadherin-associated protein α-catenin, at sites of mechanical perturbation. Studies using magnetic twisting cytometry (MTC), together with traction force microscopy (TFM) and confocal imaging identified force-activated E-cadherin-specific signals that integrate cadherin force transduction, integrin activation and cell contractility. EGFR is required for the downstream activation of PI3K and myosin-II-dependent cell stiffening. Our findings also demonstrated that α-catenin-dependent cytoskeletal remodeling at perturbed E-cadherin adhesions does not require cell stiffening. These results broaden the repertoire of E-cadherin-based force transduction mechanisms, and define the force-sensitive signaling network underlying the mechano-chemical integration of spatially segregated adhesion receptors.

Original languageEnglish (US)
Pages (from-to)1843-1854
Number of pages12
JournalJournal of cell science
Volume129
Issue number9
DOIs
StatePublished - May 1 2016

Fingerprint

Cadherins
Mechanics
Signal Transduction
Catenins
1-Phosphatidylinositol 4-Kinase
Epidermal Growth Factor Receptor
Integrins
Myosin Type II
Atomic Force Microscopy
Traction

Keywords

  • Cell signaling
  • E-cadherin
  • Integrin
  • Magnetic twisting cytometry
  • Mechanotransduction
  • Traction force microscopy

ASJC Scopus subject areas

  • Cell Biology

Cite this

E-cadherin-mediated force transduction signals regulate global cell mechanics. / Muhamed, Ismaeel; Wu, Jun; Sehgal, Poonam; Kong, Xinyu; Tajik, Arash; Wang, Ning; Leckband, Deborah E.

In: Journal of cell science, Vol. 129, No. 9, 01.05.2016, p. 1843-1854.

Research output: Contribution to journalArticle

Muhamed, Ismaeel ; Wu, Jun ; Sehgal, Poonam ; Kong, Xinyu ; Tajik, Arash ; Wang, Ning ; Leckband, Deborah E. / E-cadherin-mediated force transduction signals regulate global cell mechanics. In: Journal of cell science. 2016 ; Vol. 129, No. 9. pp. 1843-1854.
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