- Author:
- James Lawson <j.lawson@auckland.ac.nz>
- Date:
- 2009-07-23 14:53:39+12:00
- Desc:
- removed duplicate metadata, updated curation status, removed publication link from documentation
- Permanent Source URI:
- https://staging.physiomeproject.org/workspace/karagiannis_popel_2004/rawfile/f36711faffa59975c275206ce6b495793b232cc8/karagiannis_popel_2004.cellml
<?xml version='1.0' encoding='utf-8'?>
<!-- FILE : karagiannis_model_2004.xml
CREATED : 10th December 2007
LAST MODIFIED : 10th December 2007
AUTHOR : Catherine Lloyd
Bioengineering Institute
The University of Auckland
MODEL STATUS : This model conforms to the CellML 1.1 Specification.
DESCRIPTION : This file contains a CellML description of Karagiannis and Popel's 2004 mathematical model of collagen type I proteolysis by matrix metalloproteinase (MMP) 2 and membrane type I MMP during the migration of a tip endothelial cell.
CHANGES:
--><model xmlns="http://www.cellml.org/cellml/1.0#" xmlns:cmeta="http://www.cellml.org/metadata/1.0#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:bqs="http://www.cellml.org/bqs/1.0#" xmlns:cellml="http://www.cellml.org/cellml/1.0#" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" cmeta:id="karagiannis_model_2004" name="karagiannis_model_2004">
<documentation xmlns="http://cellml.org/tmp-documentation">
<article>
<articleinfo>
<title>A theoretical model of type I collagen proteolysis by matrix metalloproteinase (MMP) 2 and membrane type 1 MMP in the presence of tissue inhibitor of metalloproteinase 2</title>
<author>
<firstname>Catherine</firstname>
<surname>Lloyd</surname>
<affiliation>
<shortaffil>Bioengineering Institute, University of Auckland</shortaffil>
</affiliation>
</author>
</articleinfo>
<section id="sec_status">
<title>Model Status</title>
<para>
This version of the model has been checked in COR and OpenCell and it runs - possibly replicating the published results. The model is valid CellML and has consistent units.
</para>
</section>
<sect1 id="sec_structure">
<title>Model Structure</title>
<para>
The formation of new biological vessels requires the coordinated assembly of a proliferating syncytium of endothelial cells (EC) at different developmental stages. Angiogenesis may also be an essential mechanism of blood vessel remodelling which occurs during a diverse range of physiological processes; including tissue regeneration following injury and new vessel formation during muscle exercise. It can also occur under pathological conditions such as atherosclerosis and the vascularisation of cancerous tumours.
</para>
<para>
Matrix metalloproteinases (MMPs) are a family of enzymes responsible for the proteolytic processing of extracellular matrix (ECM) structural proteins. During angiogenesis MMPs are expressed by a single endothelial cell at the tip of the new vessel. These enzymes manifest a proteolytic activity that allows the cells of the new vessle to penetrate the ECM. In the mathematical model presented here, Karagiannis and Popel investigate the proteolytic potential of such a tip endothelial cell. The model authors suggest this model provides a foundation for future quantitative studies of angiogenesis in ECMs of different compositions. The model is described in more detail in the figure below:
</para>
<para>
The complete original paper reference is cited below:
</para>
<para>
A theoretical model of type I collagen proteolysis by matrix metalloproteinase (MMP) 2 and membrane type 1 MMP in the presence of tissue inhibitor of metalloproteinase 2, Emmanouil D. Karagiannis and Aleksander S. Popel, 2004, <emphasis>The Journal of Biological Chemistry</emphasis>, 279, 39105-39114. <ulink url="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15252025&dopt=Abstract">PubMed ID: 15252025</ulink>
</para>
<informalfigure float="0" id="fig_pathway_diagram">
<mediaobject>
<imageobject>
<objectinfo>
<title>model diagram</title>
</objectinfo>
<imagedata fileref="karagiannis_2006.png"/>
</imageobject>
</mediaobject>
<caption>A schematic diagram of the signalling pathway.</caption>
</informalfigure>
</sect1>
</article>
</documentation>
<units name="molar">
<unit units="mole"/>
<unit units="litre" exponent="-1"/>
</units>
<units name="flux">
<unit units="molar"/>
<unit units="second" exponent="-1"/>
</units>
<units name="first_order_rate_constant">
<unit units="second" exponent="-1"/>
</units>
<units name="second_order_rate_constant">
<unit units="second" exponent="-1"/>
<unit units="molar" exponent="-1"/>
</units>
<component name="environment">
<variable name="time" public_interface="out" units="second"/>
</component>
<!-- Reactions -->
<!--
<component name="v1">
<variable name="v1" public_interface="out" units="flux" />
<variable name="MT1" public_interface="in" units="molar" />
<variable name="MT1_MT1" public_interface="in" units="molar" />
<variable name="kon_MT1MT1" public_interface="in" units="second_order_rate_constant" />
<variable name="koff_MT1MT1" public_interface="in" units="first_order_rate_constant" />
<math xmlns="http://www.w3.org/1998/Math/MathML" id="1" >
<apply><eq />
<ci> v1 </ci>
<apply><minus />
<apply><times />
<ci> kon_MT1MT1 </ci>
<ci> MT1 </ci>
<ci> MT1 </ci>
</apply>
<apply><times />
<ci> koff_MT1MT1 </ci>
<ci> MT1_MT1 </ci>
</apply>
</apply>
</apply>
</math>
</component>
-->
<component name="v2">
<variable name="v2" public_interface="out" units="flux"/>
<variable name="MT1" public_interface="in" units="molar"/>
<variable name="kshed_MT1" public_interface="in" units="second_order_rate_constant"/>
<math xmlns="http://www.w3.org/1998/Math/MathML" id="2">
<apply><eq/>
<ci> v2 </ci>
<apply><minus/>
<apply><times/>
<ci> kshed_MT1 </ci>
<ci> MT1 </ci>
<ci> MT1 </ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="v3">
<variable name="v3" public_interface="out" units="flux"/>
<variable name="MT1" public_interface="in" units="molar"/>
<variable name="T2" public_interface="in" units="molar"/>
<variable name="MT1_T2" public_interface="in" units="molar"/>
<variable name="kon_MT1T2" public_interface="in" units="second_order_rate_constant"/>
<variable name="koff_MT1T2" public_interface="in" units="first_order_rate_constant"/>
<math xmlns="http://www.w3.org/1998/Math/MathML" id="3">
<apply><eq/>
<ci> v3 </ci>
<apply><minus/>
<apply><times/>
<ci> kon_MT1T2 </ci>
<ci> MT1 </ci>
<ci> T2 </ci>
</apply>
<apply><times/>
<ci> koff_MT1T2 </ci>
<ci> MT1_T2 </ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="v4">
<variable name="v4" public_interface="out" units="flux"/>
<variable name="M2p" public_interface="in" units="molar"/>
<variable name="MT1_T2" public_interface="in" units="molar"/>
<variable name="MT1_T2_M2p" public_interface="in" units="molar"/>
<variable name="kon_MT1T2M2p" public_interface="in" units="second_order_rate_constant"/>
<variable name="koff_MT1T2M2p" public_interface="in" units="first_order_rate_constant"/>
<math xmlns="http://www.w3.org/1998/Math/MathML" id="4">
<apply><eq/>
<ci> v4 </ci>
<apply><minus/>
<apply><times/>
<ci> kon_MT1T2M2p </ci>
<ci> M2p </ci>
<ci> MT1_T2 </ci>
</apply>
<apply><times/>
<ci> koff_MT1T2M2p </ci>
<ci> MT1_T2_M2p </ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="v5">
<variable name="v5" public_interface="out" units="flux"/>
<variable name="MT1" public_interface="in" units="molar"/>
<variable name="MT1_T2_M2p" public_interface="in" units="molar"/>
<variable name="MT1_T2_M2p_MT1" public_interface="in" units="molar"/>
<variable name="kon_MT1T2M2pMT1" public_interface="in" units="second_order_rate_constant"/>
<variable name="koff_MT1T2M2pMT1" public_interface="in" units="first_order_rate_constant"/>
<math xmlns="http://www.w3.org/1998/Math/MathML" id="5">
<apply><eq/>
<ci> v5 </ci>
<apply><minus/>
<apply><times/>
<ci> kon_MT1T2M2pMT1 </ci>
<ci> MT1 </ci>
<ci> MT1_T2_M2p </ci>
</apply>
<apply><times/>
<ci> koff_MT1T2M2pMT1 </ci>
<ci> MT1_T2_M2p_MT1 </ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="v6">
<variable name="v6" public_interface="out" units="flux"/>
<variable name="MT1_T2_M2p_MT1" public_interface="in" units="molar"/>
<variable name="kact_M2" public_interface="in" units="first_order_rate_constant"/>
<math xmlns="http://www.w3.org/1998/Math/MathML" id="6">
<apply><eq/>
<ci> v6 </ci>
<apply><minus/>
<apply><times/>
<ci> kact_M2 </ci>
<ci> MT1_T2_M2p_MT1 </ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="v7">
<variable name="v7" public_interface="out" units="flux"/>
<variable name="M2" public_interface="in" units="molar"/>
<variable name="T2" public_interface="in" units="molar"/>
<variable name="M2_T2" public_interface="in" units="molar"/>
<variable name="kon_M2T2" public_interface="in" units="second_order_rate_constant"/>
<variable name="koff_M2T2" public_interface="in" units="first_order_rate_constant"/>
<math xmlns="http://www.w3.org/1998/Math/MathML" id="7">
<apply><eq/>
<ci> v7 </ci>
<apply><minus/>
<apply><times/>
<ci> kon_M2T2 </ci>
<ci> M2 </ci>
<ci> T2 </ci>
</apply>
<apply><times/>
<ci> koff_M2T2 </ci>
<ci> M2_T2 </ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="v8">
<variable name="v8" public_interface="out" units="flux"/>
<variable name="M2_T2" public_interface="in" units="molar"/>
<variable name="M2_T2_star" public_interface="in" units="molar"/>
<variable name="kiso_M2T2" public_interface="in" units="first_order_rate_constant"/>
<variable name="k_iso_M2T2" public_interface="in" units="first_order_rate_constant"/>
<math xmlns="http://www.w3.org/1998/Math/MathML" id="8">
<apply><eq/>
<ci> v8 </ci>
<apply><minus/>
<apply><times/>
<ci> kiso_M2T2 </ci>
<ci> M2_T2 </ci>
</apply>
<apply><times/>
<ci> k_iso_M2T2 </ci>
<ci> M2_T2_star </ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="v9">
<variable name="v9" public_interface="out" units="flux"/>
<variable name="M2" public_interface="in" units="molar"/>
<variable name="C1" public_interface="in" units="molar"/>
<variable name="M2_C1" public_interface="in" units="molar"/>
<variable name="kon_M2C1" public_interface="in" units="second_order_rate_constant"/>
<variable name="koff_M2C1" public_interface="in" units="first_order_rate_constant"/>
<math xmlns="http://www.w3.org/1998/Math/MathML" id="9">
<apply><eq/>
<ci> v9 </ci>
<apply><minus/>
<apply><times/>
<ci> kon_M2C1 </ci>
<ci> M2 </ci>
<ci> C1 </ci>
</apply>
<apply><times/>
<ci> koff_M2C1 </ci>
<ci> M2_C1 </ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="v10">
<variable name="v10" public_interface="out" units="flux"/>
<variable name="C1" public_interface="in" units="molar"/>
<variable name="M2" public_interface="in" units="molar"/>
<variable name="km_M2C1" public_interface="in" units="molar"/>
<variable name="kcat_M2C1" public_interface="in" units="first_order_rate_constant"/>
<math xmlns="http://www.w3.org/1998/Math/MathML" id="12">
<apply><eq/>
<ci> v10 </ci>
<apply><divide/>
<apply><times/>
<ci> kcat_M2C1 </ci>
<ci> M2 </ci>
<ci> C1 </ci>
</apply>
<apply><plus/>
<ci> km_M2C1 </ci>
<ci> C1 </ci>
</apply>
</apply>
</apply>
</math>
</component>
<!--
<component name="v11">
<variable name="v11" public_interface="out" units="flux" />
<variable name="MT1" public_interface="in" units="molar" />
<variable name="C1" public_interface="in" units="molar" />
<variable name="MT1_C1" public_interface="in" units="molar" />
<variable name="kon_MT1C1" public_interface="in" units="second_order_rate_constant" />
<variable name="koff_MT1C1" public_interface="in" units="first_order_rate_constant" />
<math xmlns="http://www.w3.org/1998/Math/MathML" id="11" >
<apply><eq />
<ci> v11 </ci>
<apply><minus />
<apply><times />
<ci> kon_MT1C1 </ci>
<ci> MT1 </ci>
<ci> C1 </ci>
</apply>
<apply><times />
<ci> koff_MT1C1 </ci>
<ci> MT1_C1 </ci>
</apply>
</apply>
</apply>
</math>
</component>
-->
<component name="v12">
<variable name="v12" public_interface="out" units="flux"/>
<variable name="C1" public_interface="in" units="molar"/>
<variable name="MT1" public_interface="in" units="molar"/>
<variable name="km_MT1C1" public_interface="in" units="molar"/>
<variable name="kcat_MT1C1" public_interface="in" units="first_order_rate_constant"/>
<math xmlns="http://www.w3.org/1998/Math/MathML" id="12">
<apply><eq/>
<ci> v12 </ci>
<apply><divide/>
<apply><times/>
<ci> kcat_MT1C1 </ci>
<ci> MT1 </ci>
<ci> C1 </ci>
</apply>
<apply><plus/>
<ci> km_MT1C1 </ci>
<ci> C1 </ci>
</apply>
</apply>
</apply>
</math>
</component>
<!-- substrates -->
<component name="MT1" cmeta:id="MT1">
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/">
<rdf:Description rdf:about="MT1">
<dc:title>MT1</dc:title>
<dcterms:alternative>MT1-MMP</dcterms:alternative>
<dcterms:alternative>membrane type I matrix metalloproteinase</dcterms:alternative>
</rdf:Description>
</rdf:RDF>
<variable name="MT1" initial_value="10E-9" public_interface="out" units="molar"/>
<variable name="v2" public_interface="in" units="flux"/>
<variable name="v3" public_interface="in" units="flux"/>
<variable name="v5" public_interface="in" units="flux"/>
<variable name="v6" public_interface="in" units="flux"/>
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<variable name="time" public_interface="in" units="second"/>
<math xmlns="http://www.w3.org/1998/Math/MathML" id="13">
<apply><eq/>
<apply><diff/>
<bvar><ci> time </ci></bvar>
<ci> MT1 </ci>
</apply>
<apply><minus/>
<apply><plus/>
<ci> v2 </ci>
<ci> v6 </ci>
<ci> v12 </ci>
</apply>
<apply><plus/>
<apply><times/>
<cn cellml:units="dimensionless"> 2.0 </cn>
<ci> v2 </ci>
</apply>
<ci> v3 </ci>
<ci> v5 </ci>
<ci> v12 </ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="MT1cat" cmeta:id="MT1cat">
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/">
<rdf:Description rdf:about="MT1cat">
<dc:title>MT1cat</dc:title>
<dcterms:alternative>MT1-MMPcat</dcterms:alternative>
<dcterms:alternative>catalytic component of membrane type I matrix metalloproteinase</dcterms:alternative>
</rdf:Description>
</rdf:RDF>
<variable name="MT1cat" initial_value="0.0" public_interface="out" units="molar"/>
<variable name="v2" public_interface="in" units="flux"/>
<variable name="time" public_interface="in" units="second"/>
<math xmlns="http://www.w3.org/1998/Math/MathML" id="15">
<apply><eq/>
<apply><diff/>
<bvar><ci> time </ci></bvar>
<ci> MT1cat </ci>
</apply>
<ci> v2 </ci>
</apply>
</math>
</component>
<component name="MT1t" cmeta:id="MT1t">
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/">
<rdf:Description rdf:about="MT1t">
<dc:title>MT1t</dc:title>
<dcterms:alternative>MT1-MMPt</dcterms:alternative>
<dcterms:alternative>truncated membrane type I matrix metalloproteinase</dcterms:alternative>
</rdf:Description>
</rdf:RDF>
<variable name="MT1t" initial_value="0.0" public_interface="out" units="molar"/>
<variable name="v2" public_interface="in" units="flux"/>
<variable name="time" public_interface="in" units="second"/>
<math xmlns="http://www.w3.org/1998/Math/MathML" id="16">
<apply><eq/>
<apply><diff/>
<bvar><ci> time </ci></bvar>
<ci> MT1t </ci>
</apply>
<ci> v2 </ci>
</apply>
</math>
</component>
<component name="T2" cmeta:id="T2">
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/">
<rdf:Description rdf:about="T2">
<dc:title>T2</dc:title>
<dcterms:alternative>TIMP2</dcterms:alternative>
<dcterms:alternative>tissue inhibitor of metalloproteinases</dcterms:alternative>
</rdf:Description>
</rdf:RDF>
<variable name="T2" initial_value="4.0E-9" public_interface="out" units="molar"/>
<variable name="v3" public_interface="in" units="flux"/>
<variable name="v7" public_interface="in" units="flux"/>
<variable name="time" public_interface="in" units="second"/>
<math xmlns="http://www.w3.org/1998/Math/MathML" id="17">
<apply><eq/>
<apply><diff/>
<bvar><ci> time </ci></bvar>
<ci> T2 </ci>
</apply>
<apply><minus/>
<apply><plus/>
<ci> v3 </ci>
<ci> v7 </ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="MT1_T2" cmeta:id="MT1_T2">
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/">
<rdf:Description rdf:about="MT1_T2">
<dc:title>MT1_T2</dc:title>
<dcterms:alternative>MT1-MMP-TIMP2</dcterms:alternative>
<dcterms:alternative>membrane type I matrix metalloproteinase-tissue inhibitor of metalloproteinases complex</dcterms:alternative>
</rdf:Description>
</rdf:RDF>
<variable name="MT1_T2" initial_value="0.0" public_interface="out" units="molar"/>
<variable name="v3" public_interface="in" units="flux"/>
<variable name="v4" public_interface="in" units="flux"/>
<variable name="time" public_interface="in" units="second"/>
<math xmlns="http://www.w3.org/1998/Math/MathML" id="18">
<apply><eq/>
<apply><diff/>
<bvar><ci> time </ci></bvar>
<ci> MT1_T2 </ci>
</apply>
<apply><minus/>
<ci> v3 </ci>
<ci> v4 </ci>
</apply>
</apply>
</math>
</component>
<component name="M2p" cmeta:id="M2p">
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/">
<rdf:Description rdf:about="M2p">
<dc:title>M2p</dc:title>
<dcterms:alternative>proMMP2</dcterms:alternative>
<dcterms:alternative>proenzyme diffusible matrix metalloproteinase</dcterms:alternative>
</rdf:Description>
</rdf:RDF>
<variable name="M2p" initial_value="50.0E-9" public_interface="out" units="molar"/>
<variable name="v4" public_interface="in" units="flux"/>
<variable name="time" public_interface="in" units="second"/>
<math xmlns="http://www.w3.org/1998/Math/MathML" id="19">
<apply><eq/>
<apply><diff/>
<bvar><ci> time </ci></bvar>
<ci> M2p </ci>
</apply>
<apply><minus/>
<ci> v4 </ci>
</apply>
</apply>
</math>
</component>
<component name="MT1_T2_M2p" cmeta:id="MT1_T2_M2p">
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/">
<rdf:Description rdf:about="MT1_T2_M2p">
<dc:title>MT1_T2_M2p</dc:title>
<dcterms:alternative>MT1-MMP-TIMP2-proMMP2</dcterms:alternative>
</rdf:Description>
</rdf:RDF>
<variable name="MT1_T2_M2p" initial_value="0.0" public_interface="out" units="molar"/>
<variable name="v4" public_interface="in" units="flux"/>
<variable name="v5" public_interface="in" units="flux"/>
<variable name="time" public_interface="in" units="second"/>
<math xmlns="http://www.w3.org/1998/Math/MathML" id="20">
<apply><eq/>
<apply><diff/>
<bvar><ci> time </ci></bvar>
<ci> MT1_T2_M2p </ci>
</apply>
<apply><minus/>
<ci> v5 </ci>
<ci> v4 </ci>
</apply>
</apply>
</math>
</component>
<component name="MT1_T2_M2p_MT1" cmeta:id="MT1_T2_M2p_MT1">
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/">
<rdf:Description rdf:about="MT1_T2_M2p_MT1">
<dc:title>MT1_T2_M2p_MT1</dc:title>
<dcterms:alternative>MT1-MMP-TIMP2-proMMP2-MT1-MMP</dcterms:alternative>
</rdf:Description>
</rdf:RDF>
<variable name="MT1_T2_M2p_MT1" initial_value="0.0" public_interface="out" units="molar"/>
<variable name="v5" public_interface="in" units="flux"/>
<variable name="v6" public_interface="in" units="flux"/>
<variable name="time" public_interface="in" units="second"/>
<math xmlns="http://www.w3.org/1998/Math/MathML" id="21">
<apply><eq/>
<apply><diff/>
<bvar><ci> time </ci></bvar>
<ci> MT1_T2_M2p_MT1 </ci>
</apply>
<apply><minus/>
<ci> v5 </ci>
<ci> v6 </ci>
</apply>
</apply>
</math>
</component>
<component name="MT1_T2_star" cmeta:id="MT1_T2_star">
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/">
<rdf:Description rdf:about="MT1_T2_star">
<dc:title>MT1_T2_star</dc:title>
<dcterms:alternative>inactivated MT1-MMP-TIMP2</dcterms:alternative>
</rdf:Description>
</rdf:RDF>
<variable name="MT1_T2_star" initial_value="0.0" public_interface="out" units="molar"/>
<variable name="v6" public_interface="in" units="flux"/>
<variable name="time" public_interface="in" units="second"/>
<math xmlns="http://www.w3.org/1998/Math/MathML" id="22">
<apply><eq/>
<apply><diff/>
<bvar><ci> time </ci></bvar>
<ci> MT1_T2_star </ci>
</apply>
<apply><minus/>
<ci> v6 </ci>
</apply>
</apply>
</math>
</component>
<component name="M2" cmeta:id="M2">
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/">
<rdf:Description rdf:about="M2">
<dc:title>M2</dc:title>
<dcterms:alternative>MMP2</dcterms:alternative>
<dcterms:alternative>diffusible matrix metalloproteinase</dcterms:alternative>
</rdf:Description>
</rdf:RDF>
<variable name="M2" initial_value="30E-12" public_interface="out" units="molar"/>
<variable name="v6" public_interface="in" units="flux"/>
<variable name="v7" public_interface="in" units="flux"/>
<variable name="v9" public_interface="in" units="flux"/>
<variable name="v10" public_interface="in" units="flux"/>
<variable name="time" public_interface="in" units="second"/>
<math xmlns="http://www.w3.org/1998/Math/MathML" id="23">
<apply><eq/>
<apply><diff/>
<bvar><ci> time </ci></bvar>
<ci> M2 </ci>
</apply>
<apply><minus/>
<apply><plus/>
<ci> v6 </ci>
<ci> v10 </ci>
</apply>
<apply><plus/>
<ci> v7 </ci>
<ci> v9 </ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="M2_T2" cmeta:id="M2_T2">
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/">
<rdf:Description rdf:about="M2_T2">
<dc:title>M2_T2</dc:title>
<dcterms:alternative>MMP2-TIMP2</dcterms:alternative>
<dcterms:alternative>diffusible matrix metalloproteinase-tissue inhibitor of metalloproteinases complex</dcterms:alternative>
</rdf:Description>
</rdf:RDF>
<variable name="M2_T2" initial_value="0.0" public_interface="out" units="molar"/>
<variable name="v7" public_interface="in" units="flux"/>
<variable name="v8" public_interface="in" units="flux"/>
<variable name="time" public_interface="in" units="second"/>
<math xmlns="http://www.w3.org/1998/Math/MathML" id="24">
<apply><eq/>
<apply><diff/>
<bvar><ci> time </ci></bvar>
<ci> M2_T2 </ci>
</apply>
<apply><minus/>
<ci> v7 </ci>
<ci> v8 </ci>
</apply>
</apply>
</math>
</component>
<component name="M2_T2_star" cmeta:id="M2_T2_star">
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/">
<rdf:Description rdf:about="M2_T2_star">
<dc:title>M2_T2_star</dc:title>
<dcterms:alternative>inactivated MMP2-TIMP2</dcterms:alternative>
</rdf:Description>
</rdf:RDF>
<variable name="M2_T2_star" initial_value="0.0" public_interface="out" units="molar"/>
<variable name="v8" public_interface="in" units="flux"/>
<variable name="time" public_interface="in" units="second"/>
<math xmlns="http://www.w3.org/1998/Math/MathML" id="25">
<apply><eq/>
<apply><diff/>
<bvar><ci> time </ci></bvar>
<ci> M2_T2_star </ci>
</apply>
<ci> v8 </ci>
</apply>
</math>
</component>
<component name="M2_C1" cmeta:id="M2_C1">
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/">
<rdf:Description rdf:about="M2_C1">
<dc:title>M2_C1</dc:title>
<dcterms:alternative>MMP2-C1</dcterms:alternative>
<dcterms:alternative>diffusible matrix metalloproteinase-collagen type I complex</dcterms:alternative>
</rdf:Description>
</rdf:RDF>
<variable name="M2_C1" initial_value="0.0" public_interface="out" units="molar"/>
<variable name="v9" public_interface="in" units="flux"/>
<variable name="time" public_interface="in" units="second"/>
<math xmlns="http://www.w3.org/1998/Math/MathML" id="24">
<apply><eq/>
<apply><diff/>
<bvar><ci> time </ci></bvar>
<ci> M2_C1 </ci>
</apply>
<ci> v9 </ci>
</apply>
</math>
</component>
<component name="C1" cmeta:id="C1">
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/">
<rdf:Description rdf:about="C1">
<dc:title>C1</dc:title>
<dcterms:alternative>collagen type I</dcterms:alternative>
</rdf:Description>
</rdf:RDF>
<variable name="C1" initial_value="176E-6" public_interface="out" units="molar"/>
<variable name="v9" public_interface="in" units="flux"/>
<variable name="v10" public_interface="in" units="flux"/>
<variable name="v12" public_interface="in" units="flux"/>
<variable name="time" public_interface="in" units="second"/>
<math xmlns="http://www.w3.org/1998/Math/MathML" id="26">
<apply><eq/>
<apply><diff/>
<bvar><ci> time </ci></bvar>
<ci> C1 </ci>
</apply>
<apply><minus/>
<apply><plus/>
<ci> v9 </ci>
<ci> v10 </ci>
<ci> v12 </ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="C1D" cmeta:id="C1D">
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/">
<rdf:Description rdf:about="C1D">
<dc:title>C1D</dc:title>
<dcterms:alternative>denatured collagen type I</dcterms:alternative>
</rdf:Description>
</rdf:RDF>
<variable name="C1D" initial_value="0.0" public_interface="out" units="molar"/>
<variable name="v10" public_interface="in" units="flux"/>
<variable name="v12" public_interface="in" units="flux"/>
<variable name="time" public_interface="in" units="second"/>
<math xmlns="http://www.w3.org/1998/Math/MathML" id="27">
<apply><eq/>
<apply><diff/>
<bvar><ci> time </ci></bvar>
<ci> C1D </ci>
</apply>
<apply><plus/>
<ci> v10 </ci>
<ci> v12 </ci>
</apply>
</apply>
</math>
</component>
<!--
<component name="MT1_C1" cmeta:id="MT1_C1">
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/">
<rdf:Description rdf:about="MT1_C1">
<dc:title>MT1_C1</dc:title>
<dcterms:alternative>MT1-MMP-collagen type I</dcterms:alternative>
</rdf:Description>
</rdf:RDF>
<variable name="MT1_C1" initial_value="0.0" public_interface="out" units="molar" />
<variable name="v11" public_interface="in" units="flux" />
<variable name="v12" public_interface="in" units="flux" />
<variable name="time" public_interface="in" units="second" />
<math xmlns="http://www.w3.org/1998/Math/MathML" id="28" >
<apply><eq />
<apply><diff />
<bvar><ci> time </ci></bvar>
<ci> MT1_C1 </ci>
</apply>
<apply><minus />
<ci> v11 </ci>
<ci> v12 </ci>
</apply>
</apply>
</math>
</component>
-->
<component name="model_parameters">
<variable name="kon_M2T2" public_interface="out" initial_value="5.9E6" units="second_order_rate_constant"/>
<variable name="koff_M2T2" public_interface="out" initial_value="6.3" units="first_order_rate_constant"/>
<variable name="kiso_M2T2" public_interface="out" initial_value="33.0" units="first_order_rate_constant"/>
<variable name="k_iso_M2T2" public_interface="out" initial_value="2E-8" units="first_order_rate_constant"/>
<variable name="kon_M2C1" public_interface="out" initial_value="2.6E3" units="second_order_rate_constant"/>
<variable name="koff_M2C1" public_interface="out" initial_value="2.1E-3" units="first_order_rate_constant"/>
<variable name="kcat_M2C1" public_interface="out" initial_value="4.5E-3" units="first_order_rate_constant"/>
<variable name="kact_M2" public_interface="out" initial_value="2E-2" units="first_order_rate_constant"/>
<variable name="kon_MT1T2M2p" public_interface="out" initial_value="0.14E6" units="second_order_rate_constant"/>
<variable name="koff_MT1T2M2p" public_interface="out" initial_value="4.7E-3" units="first_order_rate_constant"/>
<variable name="kon_MT1T2M2pMT1" public_interface="out" initial_value="3E3" units="second_order_rate_constant"/>
<variable name="koff_MT1T2M2pMT1" public_interface="out" initial_value="0.9E-3" units="first_order_rate_constant"/>
<variable name="kcat_MT1C1" public_interface="out" initial_value="1.97E-3" units="first_order_rate_constant"/>
<variable name="kshed_MT1" public_interface="out" initial_value="2.8E3" units="second_order_rate_constant"/>
<variable name="kon_MT1T2" public_interface="out" initial_value="3.54E6" units="second_order_rate_constant"/>
<variable name="koff_MT1T2" public_interface="out" initial_value="20.2" units="first_order_rate_constant"/>
<variable name="km_M2C1" public_interface="out" initial_value="8.5E-6" units="molar"/>
<variable name="km_MT1C1" public_interface="out" initial_value="8.5E-6" units="molar"/>
</component>
<connection>
<map_components component_1="MT1" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="MT1cat" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="MT1t" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="T2" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="MT1_T2" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="M2p" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="MT1_T2_M2p" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="MT1_T2_M2p_MT1" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="MT1_T2_star" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="M2" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="M2_T2" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="M2_T2_star" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="M2_C1" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="C1" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="C1D" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="v2" component_2="MT1"/>
<map_variables variable_1="MT1" variable_2="MT1"/>
<map_variables variable_1="v2" variable_2="v2"/>
</connection>
<connection>
<map_components component_1="v2" component_2="model_parameters"/>
<map_variables variable_1="kshed_MT1" variable_2="kshed_MT1"/>
</connection>
<connection>
<map_components component_1="v3" component_2="MT1"/>
<map_variables variable_1="MT1" variable_2="MT1"/>
<map_variables variable_1="v3" variable_2="v3"/>
</connection>
<connection>
<map_components component_1="v3" component_2="T2"/>
<map_variables variable_1="T2" variable_2="T2"/>
<map_variables variable_1="v3" variable_2="v3"/>
</connection>
<connection>
<map_components component_1="v3" component_2="MT1_T2"/>
<map_variables variable_1="MT1_T2" variable_2="MT1_T2"/>
<map_variables variable_1="v3" variable_2="v3"/>
</connection>
<connection>
<map_components component_1="v3" component_2="model_parameters"/>
<map_variables variable_1="kon_MT1T2" variable_2="kon_MT1T2"/>
<map_variables variable_1="koff_MT1T2" variable_2="koff_MT1T2"/>
</connection>
<connection>
<map_components component_1="v4" component_2="M2p"/>
<map_variables variable_1="M2p" variable_2="M2p"/>
<map_variables variable_1="v4" variable_2="v4"/>
</connection>
<connection>
<map_components component_1="v4" component_2="MT1_T2_M2p"/>
<map_variables variable_1="MT1_T2_M2p" variable_2="MT1_T2_M2p"/>
<map_variables variable_1="v4" variable_2="v4"/>
</connection>
<connection>
<map_components component_1="v4" component_2="MT1_T2"/>
<map_variables variable_1="MT1_T2" variable_2="MT1_T2"/>
<map_variables variable_1="v4" variable_2="v4"/>
</connection>
<connection>
<map_components component_1="v4" component_2="model_parameters"/>
<map_variables variable_1="kon_MT1T2M2p" variable_2="kon_MT1T2M2p"/>
<map_variables variable_1="koff_MT1T2M2p" variable_2="koff_MT1T2M2p"/>
</connection>
<connection>
<map_components component_1="v5" component_2="MT1"/>
<map_variables variable_1="MT1" variable_2="MT1"/>
<map_variables variable_1="v5" variable_2="v5"/>
</connection>
<connection>
<map_components component_1="v5" component_2="MT1_T2_M2p"/>
<map_variables variable_1="MT1_T2_M2p" variable_2="MT1_T2_M2p"/>
<map_variables variable_1="v5" variable_2="v5"/>
</connection>
<connection>
<map_components component_1="v5" component_2="MT1_T2_M2p_MT1"/>
<map_variables variable_1="MT1_T2_M2p_MT1" variable_2="MT1_T2_M2p_MT1"/>
<map_variables variable_1="v5" variable_2="v5"/>
</connection>
<connection>
<map_components component_1="v5" component_2="model_parameters"/>
<map_variables variable_1="kon_MT1T2M2pMT1" variable_2="kon_MT1T2M2pMT1"/>
<map_variables variable_1="koff_MT1T2M2pMT1" variable_2="koff_MT1T2M2pMT1"/>
</connection>
<connection>
<map_components component_1="v6" component_2="MT1_T2_M2p_MT1"/>
<map_variables variable_1="MT1_T2_M2p_MT1" variable_2="MT1_T2_M2p_MT1"/>
<map_variables variable_1="v6" variable_2="v6"/>
</connection>
<connection>
<map_components component_1="v6" component_2="model_parameters"/>
<map_variables variable_1="kact_M2" variable_2="kact_M2"/>
</connection>
<connection>
<map_components component_1="v7" component_2="M2"/>
<map_variables variable_1="M2" variable_2="M2"/>
<map_variables variable_1="v7" variable_2="v7"/>
</connection>
<connection>
<map_components component_1="v7" component_2="T2"/>
<map_variables variable_1="T2" variable_2="T2"/>
<map_variables variable_1="v7" variable_2="v7"/>
</connection>
<connection>
<map_components component_1="v7" component_2="M2_T2"/>
<map_variables variable_1="M2_T2" variable_2="M2_T2"/>
<map_variables variable_1="v7" variable_2="v7"/>
</connection>
<connection>
<map_components component_1="v7" component_2="model_parameters"/>
<map_variables variable_1="kon_M2T2" variable_2="kon_M2T2"/>
<map_variables variable_1="koff_M2T2" variable_2="koff_M2T2"/>
</connection>
<connection>
<map_components component_1="v8" component_2="M2_T2"/>
<map_variables variable_1="M2_T2" variable_2="M2_T2"/>
<map_variables variable_1="v8" variable_2="v8"/>
</connection>
<connection>
<map_components component_1="v8" component_2="M2_T2_star"/>
<map_variables variable_1="M2_T2_star" variable_2="M2_T2_star"/>
<map_variables variable_1="v8" variable_2="v8"/>
</connection>
<connection>
<map_components component_1="v8" component_2="model_parameters"/>
<map_variables variable_1="kiso_M2T2" variable_2="kiso_M2T2"/>
<map_variables variable_1="k_iso_M2T2" variable_2="k_iso_M2T2"/>
</connection>
<connection>
<map_components component_1="v9" component_2="M2"/>
<map_variables variable_1="M2" variable_2="M2"/>
<map_variables variable_1="v9" variable_2="v9"/>
</connection>
<connection>
<map_components component_1="v9" component_2="C1"/>
<map_variables variable_1="C1" variable_2="C1"/>
<map_variables variable_1="v9" variable_2="v9"/>
</connection>
<connection>
<map_components component_1="v9" component_2="M2_C1"/>
<map_variables variable_1="M2_C1" variable_2="M2_C1"/>
<map_variables variable_1="v9" variable_2="v9"/>
</connection>
<connection>
<map_components component_1="v9" component_2="model_parameters"/>
<map_variables variable_1="kon_M2C1" variable_2="kon_M2C1"/>
<map_variables variable_1="koff_M2C1" variable_2="koff_M2C1"/>
</connection>
<connection>
<map_components component_1="v10" component_2="M2"/>
<map_variables variable_1="M2" variable_2="M2"/>
<map_variables variable_1="v10" variable_2="v10"/>
</connection>
<connection>
<map_components component_1="v10" component_2="C1"/>
<map_variables variable_1="C1" variable_2="C1"/>
<map_variables variable_1="v10" variable_2="v10"/>
</connection>
<connection>
<map_components component_1="v10" component_2="model_parameters"/>
<map_variables variable_1="km_M2C1" variable_2="km_M2C1"/>
<map_variables variable_1="kcat_M2C1" variable_2="kcat_M2C1"/>
</connection>
<connection>
<map_components component_1="v10" component_2="C1D"/>
<map_variables variable_1="v10" variable_2="v10"/>
</connection>
<connection>
<map_components component_1="v12" component_2="MT1"/>
<map_variables variable_1="MT1" variable_2="MT1"/>
<map_variables variable_1="v12" variable_2="v12"/>
</connection>
<connection>
<map_components component_1="v12" component_2="C1"/>
<map_variables variable_1="C1" variable_2="C1"/>
<map_variables variable_1="v12" variable_2="v12"/>
</connection>
<connection>
<map_components component_1="v12" component_2="model_parameters"/>
<map_variables variable_1="km_MT1C1" variable_2="km_MT1C1"/>
<map_variables variable_1="kcat_MT1C1" variable_2="kcat_MT1C1"/>
</connection>
<connection>
<map_components component_1="v12" component_2="C1D"/>
<map_variables variable_1="v12" variable_2="v12"/>
</connection>
<connection>
<map_components component_1="v6" component_2="MT1"/>
<map_variables variable_1="v6" variable_2="v6"/>
</connection>
<connection>
<map_components component_1="v2" component_2="MT1cat"/>
<map_variables variable_1="v2" variable_2="v2"/>
</connection>
<connection>
<map_components component_1="v2" component_2="MT1t"/>
<map_variables variable_1="v2" variable_2="v2"/>
</connection>
<connection>
<map_components component_1="v6" component_2="MT1_T2_star"/>
<map_variables variable_1="v6" variable_2="v6"/>
</connection>
<connection>
<map_components component_1="v6" component_2="M2"/>
<map_variables variable_1="v6" variable_2="v6"/>
</connection>
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<rdf:Bag rdf:about="rdf:#19973935-340d-4b46-8263-8ddb4e920338">
<rdf:li>collagen</rdf:li>
<rdf:li>matrix metalloproteinase</rdf:li>
<rdf:li>signal transduction</rdf:li>
<rdf:li>cerebral aneurysm</rdf:li>
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<bqs:Pubmed_id>15252025</bqs:Pubmed_id>
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The University of Auckland, Bioengineering Institute
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Journal of Biological Chemistry
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This is a CellML description of Karagiannis and Popel's 2004 mathematical model of collagen type I proteolysis by matrix metalloproteinase (MMP) 2 and membrane type I MMP during the migration of a tip endothelial cell.
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A theoretical model of type I collagen proteolysis by matrix metalloproteinase (MMP) 2 and membrane type 1 MMP in the presence of tissue inhibitor of metalloproteinase 2
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<bqs:volume>279</bqs:volume>
<bqs:first_page>39105</bqs:first_page>
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<vCard:Given>Aleksander</vCard:Given>
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<dcterms:W3CDTF>2004-09-10</dcterms:W3CDTF>
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Karagiannis and Popel's 2004 mathematical model of collagen type I proteolysis by matrix metalloproteinase (MMP) 2 and membrane type I MMP during the migration of a tip endothelial cell.
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