Research

One-dimensional Elastic Continuum Model of Enterocyte Layer Migration

Necrotizing enterocolitis is the leading cause of death from gastrointestinal disease in preterm infants. It results from an injury to the mucosal lining of the intestine, leading to translocation of bacteria and endotoxin into the circulation. Intestinal mucosal defects are repaired by the process of intestinal restitution, during which enterocytes migrate from healthy areas to sites of injury. In this article, we develop a mathematical model of migration of enterocytes during experimental necrotizing enterocolitis.
 
The model is based on a novel assumption of elastic deformation of the cell layer and incorporates the following effects: i), mobility promoting force due to lamellipod formation, ii), mobility impeding adhesion to the cell matrix, and iii), enterocyte proliferation.
 
Our model successfully reproduces the behavior observed for enterocyte migration on glass coverslips, namely the dependence of migration speed on the distance from the wound edge, and the finite propagation distance in the absence of proliferation that results in an occasional failure to close the wound. It also qualitatively reproduces the dependence of migration speed on integrin concentration. The model is applicable to the closure of a wound with a linear edge and, after calibration with experimental data, could be used to predict the effect of chemical agents on mobility, adhesion, and proliferation of enterocytes.

 
Snapshots of IEC-6 cells migrating on a glass coverslip at (A) t ¼ 0, (B) t ¼ 5 h, and (C) t ¼ 10 h. The tracked cells are labeled as U1 … U10 and L1 … L10.

 
The observed paths of cells U1 … U10 and L1 … L10 from the previous figure. The positions of edges at t ¼ 0 are indicated by solid lines. The direction of motion, along which traveled distances were measured, is shown as a dash-dotted line. Elastic Model of Cell Layer Migration 3749.
 
Authors
Mi Q, Swigon D, Rivière B, Cetin S, Vodovotz Y, Hackam DJ
Biophys J
2007 Dec 1

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January 18, 2011
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