Intercellular Adhesion Stiffness Moderates Cell Decoupling as a Function of Substrate Stiffness.

Area of Science:

• Cell biology
• Biophysics
• Computational modeling

Background:

• Cell-cell and cell-substrate interactions are crucial for tissue formation and function.
• Mechanosensing mechanisms regulate both intercellular communication and cell-matrix adhesion.

Purpose of the Study:

• To develop a computational model of cell-cell and cell-substrate interactions.
• To investigate the role of mechanosensing in these interactions and phenomena like cell decoupling.

Main Methods:

• Utilized the discrete element method to create a 3D computational model of a cell pair.
• Explicitly modeled mechanosensing components: focal adhesions, adherens junctions, and contractile stress fibers.
• Simulated traction maps and compared them with experimental traction force microscopy data.

Main Results:

• The model accurately reproduced the substrate stiffness dependence of traction distribution, contractile moment, intercellular force, and focal adhesion numbers.
• Successfully simulated cell decoupling, where cells exert forces independently at increased substrate stiffness.
• Identified competition between fiber-adhesion configurations as the molecular driver of decoupling.

Conclusions:

• Mechanosensing mechanisms drive competition between cell-substrate and cell-cell adhesion.
• Increasing substrate stiffness favors cell-substrate adhesion, leading to cell decoupling.
• The model provides a framework for understanding the biophysical basis of cell-cell and cell-substrate interactions.