Substrate stiffness and mechanical stress due to intercellular cooperativity guides tissue structure

Area of Science:

• Cell Biology
• Biophysics
• Tissue Engineering

Background:

• Tissue morphogenesis relies on balancing cell proliferation and apoptosis.
• Cells actively sense and respond to the mechanical properties of their extracellular matrix (ECM).
• Intercellular interactions and substrate stiffness are critical for tissue self-organization.

Purpose of the Study:

• To investigate how cell proliferation and apoptosis influence tissue structure dynamics.
• To characterize emergent tissue patterns resulting from cell-ECM interactions.
• To understand the role of ECM stiffness and intercellular cooperativity in cell viability.

Main Methods:

• Simulated a 2D elastic fiber-network model of cell-ECM composites.
• Analyzed tissue pattern formation during simulated cell proliferation and apoptosis.
• Quantified the relationship between ECM stiffness, intercellular cooperativity, and cell viability.

Main Results:

• Cell viability is dependent on cell-induced effective ECM stiffness and intercellular cooperativity.
• Heterogeneous proliferation and apoptosis, leading to finger-like protrusions, are promoted by cell cycle duration and ECM stress.
• Wound healing is impaired on compliant or collagen-depleted ECM.

Conclusions:

• Cell-ECM mechanical interactions govern tissue morphogenesis and pattern formation.
• ECM stiffness and cellular cooperation are key regulators of cell fate and tissue remodeling.
• Impaired wound healing on altered ECM highlights the importance of mechanical cues in tissue repair.