One-dimensional elastic continuum model of enterocyte layer migration

Area of Science:

• Mathematical modeling
• Gastroenterology
• Developmental biology

Background:

• Necrotizing enterocolitis (NEC) is a critical gastrointestinal disease in preterm infants, often resulting from intestinal mucosal injury.
• Bacterial translocation and endotoxemia follow mucosal damage, leading to severe complications.
• Intestinal restitution, driven by enterocyte migration, is key to repairing mucosal defects.

Purpose of the Study:

• To develop a mathematical model simulating enterocyte migration during necrotizing enterocolitis.
• To incorporate key factors influencing cell migration: mobility forces, adhesion, and proliferation.
• To validate the model against experimental observations of wound healing.

Main Methods:

• Development of a novel mathematical model based on elastic cell layer deformation.
• Inclusion of forces promoting mobility (lamellipod formation) and impeding adhesion.
• Integration of enterocyte proliferation as a factor in wound closure.
• Comparison of model predictions with experimental data on enterocyte migration speed and wound closure.

Main Results:

• The model accurately reproduces the observed dependence of migration speed on distance from the wound edge.
• It captures the finite propagation distance and occasional wound closure failure in the absence of proliferation.
• Qualitative agreement was achieved for migration speed's dependence on integrin concentration.

Conclusions:

• The developed mathematical model effectively simulates enterocyte migration in the context of necrotizing enterocolitis.
• The model provides insights into factors governing wound healing, including cell mobility, adhesion, and proliferation.
• It offers a framework for predicting the impact of therapeutic interventions on enterocyte behavior and wound closure.