Mechanical Heterogeneity in Tissues Promotes Rigidity and Controls Cellular Invasion

Area of Science:

• Biophysics
• Materials Science
• Computational Biology

Background:

• Epithelial tissues exhibit complex mechanical properties influenced by individual cell mechanics.
• Understanding how cell-level heterogeneity impacts tissue-scale behavior is crucial for developmental biology and disease modeling.

Purpose of the Study:

• To investigate the role of cell-level mechanical heterogeneity in epithelial tissue rigidity.
• To determine the relationship between heterogeneity, tissue mechanical states (fluid vs. solid), and tumor invasion.

Main Methods:

• Utilized a vertex-based computational model to simulate epithelial tissues.
• Introduced heterogeneity in cell shape index (p0) to tune single-cell stiffness.
• Analyzed shear modulus, scaling laws, and identified critical thresholds for rigidity.

Main Results:

• Mechanical heterogeneity consistently increases epithelial layer rigidity by enhancing shear modulus.
• A universal scaling variable (fr) and threshold (fr*) were identified, separating fluid from solid tissue states.
• Rigidity onset occurs independently and below the contact percolation threshold, revealing distinct solid states.
• Increased tissue rigidity impedes tumor invasion, though invasion is possible in intermediate heterogeneous states with intermittent dynamics.

Conclusions:

• Cell-level mechanical heterogeneity is a key determinant of epithelial tissue rigidity and mechanical phase transitions.
• The findings separate rigidity and percolation phenomena, offering new insights into solid-like behaviors in biological tissues.
• Tissue mechanical properties influenced by heterogeneity significantly impact tumor invasion dynamics, suggesting potential therapeutic targets.