Geometric control by active mechanics of epithelial gap closure

Area of Science:

• Biophysics
• Cell Biology
• Mathematical Biology

Background:

• Epithelial wound healing is a crucial self-repair process for tissue integrity.
• Understanding the biophysical mechanisms driving gap closure is essential.

Purpose of the Study:

• To develop a novel diffuse interface model for epithelial gap closure.
• To investigate the roles of lamellipodia-driven crawling and actomyosin tension in closure dynamics.

Main Methods:

• Derivation of a diffuse interface model using a variational principle in non-equilibrium thermodynamics.
• Incorporation of active features (lamellipodia, actomyosin cable) as Korteweg forces.
• Asymptotic analysis to derive sharp interface limits and interfacial relations (Gibbs-Thompson).
• Finite element simulations to validate model predictions against experimental data.

Main Results:

• The model accurately predicts closure dynamics and edge morphology, matching experimental observations.
• Simulations show good qualitative agreement with traction force microscopy measurements.
• Identified the geometrical control of gap closure by active, chemically activated forces at the gap edge.

Conclusions:

• The diffuse interface approach provides a robust framework for modeling epithelial wound healing.
• Active cellular forces, particularly supracellular tension, play a significant role in regulating wound closure.
• The study offers insights into the interplay between mechanics and chemistry in biological self-repair.