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

Area of Science:

• Cell Biology
• Biophysics
• Mechanobiology

Background:

• E-cadherin mediates cell-cell adhesion and plays a role in mechanotransduction.
• Cellular responses to mechanical forces involve complex signaling pathways and cytoskeletal rearrangements.
• Integrin adhesions and cadherin adhesions are critical for cell structure and signaling.

Purpose of the Study:

• To elucidate an E-cadherin-based force-transduction pathway.
• To understand the roles of epidermal growth factor receptor (EGFR) and phosphoinositide 3-kinase (PI3K) in this pathway.
• To investigate the integration of cadherin force transduction, integrin activation, and cell contractility.

Main Methods:

• Magnetic twisting cytometry (MTC) to measure cell mechanics.
• Traction force microscopy (TFM) to map cellular forces.
• Confocal imaging to visualize protein localization and interactions.
• Biochemical assays to assess signaling pathway activation.

Main Results:

• Identified an E-cadherin-based pathway requiring EGFR, PI3K, and new integrin adhesions for changes in cell mechanics.
• Demonstrated that EGFR is essential for PI3K activation and myosin-II-dependent cell stiffening.
• Showed that α-catenin-dependent cytoskeletal remodeling at perturbed adhesions occurs independently of cell stiffening.
• Revealed force-activated E-cadherin signals integrating cadherin force transduction, integrin activation, and cell contractility.

Conclusions:

• Broadened the understanding of E-cadherin-based force transduction mechanisms.
• Defined a force-sensitive signaling network integrating spatially segregated adhesion receptors.
• Highlighted the interplay between mechanical forces, adhesion dynamics, and signaling pathways in regulating cell mechanics.