Diffusion of MMPs on the Surface of Collagen Fibrils The Mobile Cell Surface – Collagen Substratum Interface 英文参考文献.docVIP
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Diffusion of MMPs on the Surface of Collagen Fibrils The Mobile Cell Surface – Collagen Substratum Interface 英文参考文献
DiffusionofMMPsontheSurfaceofCollagenFibrils:The
MobileCellSurface–CollagenSubstratumInterface
IvanE.Collier1,WesleyLegant4,BarryMarmer1,OlgaLubman3,SaveezSaffarian5,TetsuroWakatsuki6,
ElliotElson2,GregoryI.Goldberg1,2*
1Division of Dermatology, Department of Medicine, Washington University School of Medicine, Saint Louis, Missouri, United States of America, 2Department of
Biochemistry and Molecular Biophysics, Washington University School of Medicine, Saint Louis, Missouri, United States of America, 3Department of Pathology,
Washington University School of Medicine, Saint Louis, Missouri, United States of America, 4Department of Bioengineering, University of Pennsylvania, Philadelphia,
Pennsylvania, United States of America, 5Department of Physics, University of Utah, Salt Lake City, Utah, United States of America, 6Department of Physiology,
BiotechnologyandBioengineeringCenter,MedicalCollegeofWisconsin,Milwaukee,Wisconsin,UnitedStatesofAmerica
Abstract
RemodelingoftheextracellularmatrixcatalyzedbyMMPsiscentraltomorphogeneticphenomenaduringdevelopment
and wound healing as well as in numerous pathologic conditions such as fibrosis and cancer. We have previously
demonstrated that secreted MMP-2 is tethered to the cell surface and activated by MT1-MMP/TIMP-2-dependent
mechanism. The resulting cell-surface collagenolytic complex (MT1-MMP)2/TIMP-2/MMP-2 can initiate (MT1-MMP) and
complete(MMP-2)degradationofanunderlyingcollagenfibril.Thefollowingquestionremained:Whatisthemechanismof
substraterecognitioninvolvingthetwostructuresofrelativelyrestrictedmobility,thecellsurfaceenzymaticcomplexanda
collagen fibril embedded in the ECM? Here we demonstrate that all the components of the complex are capable of
processivemovementonasurfaceofthecollagenfibril.ThemechanismofMT1-MMPmovementisabiaseddiffusionwith
thebiascomponentdependentontheproteolysisofitssubstrate,notadenosinetriphosphate(ATP)hydrolysis.Itissimilar
tothatoftheMMP-1Brownianratchetwedescribedearlier.Inaddition,bot
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