Computational model to probe cellular mechanics during epithelial-mesenchymal transition.

Area of Science:

• Cell Biology
• Biophysics
• Computational Biology

Background:

• Epithelial to mesenchymal transition (EMT) is crucial in development and cancer metastasis.
• Current research often focuses on molecular markers, neglecting mechanical changes.
• A gap exists in understanding the role of cellular mechanics in EMT.

Purpose of the Study:

• To quantitatively model population-level effects of single-cell changes during EMT.
• To investigate the impact of cellular molecular processes on EMT using a computational approach.
• To explore the interplay between mechanical forces and cell-cell adhesion in EMT.

Main Methods:

• Developed a computational model combining single-cell migration and agent-based population models.
• Simulated epithelium disruption on an extracellular matrix using interaction forces.
• Varied protrusion force magnitude and E-cadherin concentration, tracking cell behavior over 3 days.

Main Results:

• High protrusion force or reduced E-cadherin concentration can induce EMT.
• Epithelium disruption morphology influences the number of invasive cells.
• Clustering of epithelial layers can impede further cell exodus.

Conclusions:

• Mechanical factors like protrusion force and cell-cell adhesion are critical drivers of EMT.
• The spatial organization of epithelial disruption affects invasive potential.
• This study provides a quantitative systems-level understanding of EMT mechanisms.