Epithelial Cell-Like Elasticity Modulates Actin-Dependent E-Cadherin Adhesion Organization.

Area of Science:

• Cell biology
• Biophysics
• Biomaterials science

Background:

• E-cadherin mediates cell-to-cell adhesion and mechanical coupling in epithelial tissues.
• E-cadherin functions as a mechanosensor, but its response to varying epithelial cell stiffness remains unclear.
• Epithelial cells exhibit Young's moduli in the sub-kPa to few-kPa range, with cancer cells often being softer.

Purpose of the Study:

• To investigate if E-cadherin adhesions can differentially sense stiffness within the physiological range of epithelial cells.
• To determine how E-cadherin adhesions organize in response to varying substrate elasticity.
• To explore the role of the actin cytoskeleton in modulating E-cadherin adhesion organization based on substrate stiffness.

Main Methods:

• Fabrication of oriented E-cadherin-coated soft silicone substrates with distinct elastic moduli (0.3 kPa and 2.4 kPa).
• Utilized substrates with similar viscous moduli to isolate the effect of elasticity.
• Microscopic analysis of E-cadherin adhesion organization and actin cytoskeleton architecture.

Main Results:

• E-cadherin adhesions differentially organized based on substrate elasticity, mimicking epithelial cell stiffness.
• Actin cytoskeleton influenced adhesion morphology: irregular shapes at actin density foci and linear shapes at actin bundle ends.
• Linear E-cadherin adhesions associated with radial actin were more prevalent on stiffer (2.4 kPa) substrates compared to softer (0.3 kPa) ones.
• Total E-cadherin amount per cell remained similar across different stiffness levels.

Conclusions:

• E-cadherin adhesion distribution is modulated by epithelial cell-like elasticity through actin density and architecture.
• Altered E-cadherin organization due to stiffness variations has implications for diseases like carcinomas with modified cell elasticity.