BIOPHYSICAL THEORY AND MODELING |
One-dimensional Elastic Continuum Model of Enterocyte Layer Migration
Qi Mi 1, David Swigon 1*, Beatrice Riviere 1, Selma Cetin 2, Yoram Vodovotz 1 and David J. Hackam 2
1 University of Pittsburgh
2 Children's Hospital of Pittsburgh
* To whom correspondence should be addressed. E-mail: swigon{at}pitt.edu.
Submitted on May 9, 2007
Revised on June 8, 2007
Accepted on 9 July 2007
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Abstract |
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Necrotizing enterocolitis (NEC) 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 paper, we develop a mathematical model of migration of enterocytes during experimental NEC. 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 which 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.
Key Words:
elasticity, integrins, mathematical model, necrotizing enterocolitis, wound healing
