An extended Cellular Potts Model analyzing a wound healing assay

Area of Science:

• Computational Biology
• Cell Biology
• Biophysics

Background:

• Wound healing is a complex biological process involving cell migration.
• In vitro assays are crucial for studying cellular behavior during healing.
• Quantifying cell movement and its determinants is essential for understanding wound closure.

Purpose of the Study:

• To develop and validate a Cellular Potts Model (CPM) for analyzing in vitro wound-healing assays.
• To quantify the invasive capacity of cell populations and individual cell movement parameters (velocity, direction, displacement).
• To investigate the influence of extracellular matrix properties and cell characteristics on wound healing dynamics.

Main Methods:

• Development of a Cellular Potts Model (CPM) to simulate in vitro wound healing.
• Quantification of cell population invasiveness and single-cell movement parameters.
• Simulation of cell behavior on undifferentiated and two-component (fibrous) substrates.
• Analysis of the impact of cell elasticity, intercellular adhesion, fiber density, and cell-fiber adhesion on migration and closure.

Main Results:

• The CPM successfully reproduced and analyzed in vitro wound-healing assays, capturing cell migration dynamics.
• For undifferentiated matrices, increased cell elasticity was predicted to maximize healing, outperforming reduced intercellular adhesion.
• On fibrous substrates, fiber number and cell-fiber adhesiveness showed biphasic effects on speed and closure rate, while network topology influenced directional movement.

Conclusions:

• The developed CPM is a valuable tool for quantifying cell migration and analyzing wound healing processes.
• Cell elasticity plays a critical role in wound closure on homogeneous matrices.
• The structure and composition of fibrous extracellular matrices significantly modulate cell migration and wound closure rates.