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.
Mi
Qi
Q
Department of Mathematics, Center for Inflammation and Regeneration Modeling, McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Swigon
David
D
Rivière
Béatrice
B
Cetin
Selma
S
Vodovotz
Yoram
Y
Hackam
David J
DJ
D000818:Animals; D002448:Cell Adhesion; D002449:Cell Aggregation; D002465:Cell Movement; D003198:Computer Simulation; D004548:Elasticity; D020345:Enterocolitis, Necrotizing / Q000473:pathology* / Q000503:physiopathology*; D020895:Enterocytes / Q000473:pathology* / Q000502:physiology*; D006801:Humans; D007413:Intestinal Mucosa / Q000473:pathology* / Q000503:physiopathology*; D040542:Mechanotransduction, Cellular; D008954:Models, Biological
Biorheology. 2005;42(5):321-33
16308464
Semin Pediatr Surg. 2005 Aug;14(3):181-90
16084406
Shock. 2007 Feb;27(2):124-33
17224785
Immunol Res. 2006;36(1-3):237-45
17337784
J Pediatr Surg. 2007 Mar;42(3):445-53
17336179
Am J Physiol Gastrointest Liver Physiol. 2007 May;292(5):G1347-58
17272518
Gastroenterology. 2007 Jun;132(7):2395-411
17570214
Wound Repair Regen. 2007 Sep-Oct;15(5):671-82
17971013
Exp Cell Res. 2000 Nov 25;261(1):69-74
11082276
Wound Repair Regen. 2001 Jul-Aug;9(4):278-86
11679136
J Cell Biol. 2001 Dec 24;155(7):1319-32
11756480
Pediatr Dev Pathol. 2003 Jan-Feb;6(1):6-23
12424605
Crit Care Med. 2003 Aug;31(8 Suppl):S532-7
12907883
J Biol Chem. 2004 Jun 4;279(23):24592-600
15169791
Surgery. 2004 Aug;136(2):375-83
15300204
Biosystems. 2004 Aug-Oct;76(1-3):89-100
15351133
IEEE Trans Nanobioscience. 2004 Sep;3(3):153-63
15473067
Acta Ophthalmol (Copenh). 1979;57(6):945-58
546009
Invest Ophthalmol Vis Sci. 1985 Apr;26(4):443-9
3980166
IMA J Math Appl Med Biol. 1984;1(1):51-75
6600092
Virchows Arch A Pathol Anat Histopathol. 1988;414(1):77-81
3144806
Proc Biol Sci. 1990 Jul 23;241(1300):29-36
1978332
Biophys J. 1991 Jul;60(1):15-37
1883934
J Surg Res. 1993 Aug;55(2):233-47
8412105
J Math Biol. 1993;31(7):703-16
8245731
J Theor Biol. 1995 Nov 21;177(2):113-28
8558902
Nature. 1997 Feb 6;385(6616):537-40
9020360
Trends Cell Biol. 1998 Feb;8(2):51-4
9695809
Gastroenterology. 2005 Apr;128(4):1012-22
15825082
Semin Pediatr Surg. 2005 Aug;14(3):167-74
16084404
Semin Pediatr Surg. 2005 Aug;14(3):175-80
16084405
J Cell Biol. 2006 Sep 11;174(6):767-72
16966418