title: Development of a mathematical model to describe the transport of monocyte chemoattractant protein-1 through a three-dimensional collagen matrix.
abstract: BACKGROUND
  Monocyte chemoattractant protein-1 is a bioactive molecule that is expressed in significant amounts in all stages of atherosclerosis. The role of monocyte chemoattractant protein-1 in this disease is to recruit monocytes across the endothelium and into the arterial tissue. Eventually, the monocytes differentiate into cholesterol-engorged macrophages called "foam cells" that result in atherosclerotic plaque formation. The mechanism that monocyte chemoattractant protein-1 uses to mediate monocyte transendothelial migration is believed to be via its concentration gradient. However, the formation of the monocyte chemoattractant protein-1 concentration gradient in the extracellular matrix is still poorly understood.
  
  
  METHODS
  A three-dimensional in vitro vascular tissue model has been developed to study the cellular mechanisms involved in the early stages of atherosclerosis. In the present study, a mathematical model is used to determine the gradient of monocyte chemoattractant protein-1 in the collagen matrix of the three-dimensional in vitro vascular tissue model. Experiments were performed to investigate the stability of monocyte chemoattractant protein-1 and the interaction between monocyte chemoattractant protein-1 and the collagen matrix.
  
  
  CONCLUSIONS
  Monocyte chemoattractant protein-1 is stable for at least 24 h under experimental conditions and monocyte chemoattractant protein-1 interacts with the collagen matrix. The diffusion coefficient for the transport of monocyte chemoattractant protein-1 in the collagen matrix and the rate constant for the binding of monocyte chemoattractant protein-1 to collagen were determined to be 0.108 mm(2) h(-1) and 0.858 h(-1), respectively. Numerical results from the model indicate that the concentration gradients of both soluble and matrix-bound (or static) monocyte chemoattractant protein-1 are formed inside the collagen matrix.
authors.affiliation: School of Chemical Engineering, Oklahoma State University, 423 Engineering North, Stillwater, OK 74078, USA.
authors.forename: Krisada
authors.initials: K
authors.lastname: Leemasawatdigul
authors.forename: Heather
authors.initials: H
authors.lastname: Gappa-Fahlenkamp
mesh_terms: D018929:Cell Culture Techniques / Q000379:methods*; D002465:Cell Movement; D018932:Chemokine CCL2 / Q000378:metabolism*; D003094:Collagen / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D021381:Protein Transport; D011994:Recombinant Proteins; D023822:Tissue Engineering / Q000379:methods*
chemical_list: D018932:Chemokine CCL2; D011994:Recombinant Proteins; D003094:Collagen
references.citation: Clin Exp Immunol. 2002 Mar;127(3):436-44
references.pmid: 11966759
references.citation: Blood. 2002 Aug 15;100(4):1160-7
references.pmid: 12149192
references.citation: Arthritis Rheum. 2006 Jan;54(1):214-25
references.pmid: 16385517
references.citation: Am Heart J. 1999 Nov;138(5 Pt 2):S419-20
references.pmid: 10539839
references.citation: J Exp Med. 2005 Dec 19;202(12):1649-58
references.pmid: 16352737
references.citation: J Clin Invest. 1997 Dec 1;100(11):2680-90
references.pmid: 9389731
references.citation: Exp Toxicol Pathol. 2007 Apr;58(5):277-83
references.pmid: 17145177
references.citation: J Clin Invest. 1991 Dec;88(6):2039-46
references.pmid: 1752961
references.citation: Clin Immunol. 2001 Apr;99(1):43-52
references.pmid: 11286540
references.citation: Eur J Immunol. 1999 Feb;29(2):700-12
references.pmid: 10064088
references.citation: Mol Cell. 1998 Aug;2(2):275-81
references.pmid: 9734366
references.citation: J Exp Med. 1996 Sep 1;184(3):799-802
references.pmid: 9064339
references.citation: J Mol Histol. 2010 Dec;41(6):367-77
references.pmid: 20936527
references.citation: Science. 1991 Oct 4;254(5028):99-102
references.pmid: 1718038
references.citation: Arterioscler Thromb Vasc Biol. 1999 Sep;19(9):2085-93
references.pmid: 10479649
references.citation: Nature. 1998 Aug 27;394(6696):894-7
references.pmid: 9732872
references.citation: Biomaterials. 2005 Aug;26(24):5048-63
references.pmid: 15769541
references.citation: Clin Exp Immunol. 1999 Oct;118(1):35-40
references.pmid: 10540157
references.citation: J Immunol. 1994 Dec 1;153(11):4899-906
references.pmid: 7525718
references.citation: Eur J Immunol. 1993 Jan;23(1):303-6
references.pmid: 8419183
references.citation: Antimicrob Agents Chemother. 2004 Jul;48(7):2538-43
references.pmid: 15215106
references.citation: Proc Natl Acad Sci U S A. 1991 Jun 15;88(12):5252-6
references.pmid: 2052604
references.citation: Arterioscler Thromb Vasc Biol. 1996 Jul;16(7):831-42
references.pmid: 8673557
references.citation: Curr Opin Lipidol. 1998 Oct;9(5):397-405
references.pmid: 9812193
references.citation: In Vitro Cell Dev Biol Anim. 2009 May-Jun;45(5-6):234-42
references.pmid: 19184250
references.citation: Atherosclerosis. 1993 May;100(2):237-48
references.pmid: 8357356
references.citation: Toxicol Lett. 2000 Mar 15;112-113:519-29
references.pmid: 10720775
references.citation: Blood. 2004 Mar 15;103(6):2417-26
references.pmid: 14615370
references.citation: Immunology. 1997 Dec;92(4):512-8
references.pmid: 9497493
references.citation: J Leukoc Biol. 1995 Oct;58(4):438-44
references.pmid: 7561520
references.citation: J Immunol. 1995 Oct 1;155(7):3610-8
references.pmid: 7561060
references.citation: Cytometry A. 2011 Apr;79(4):256-62
references.pmid: 21412982
references.citation: J Am Soc Nephrol. 2008 Sep;19(9):1712-20
references.pmid: 18508964
references.citation: Curr Biol. 1994 May 1;4(5):394-400
references.pmid: 7922353
references.citation: Transfusion. 2001 Mar;41(3):378-81
references.pmid: 11274594
references.citation: Biophys J. 2006 Jul 1;91(1):113-21
references.pmid: 16603487