FMIPABiology DepartmentBrawijaya UniversityEXTRA CELLULAR MATRIXCELL BIOLOGYDrs. Sofy PERMANA, MSc.,DSc. TOPICS=TOPICS=Matriks Ektraseluler Structures , Organization & Functions, Wound healing Introd!tionIntrod!tionThis lecture introduces the materials lying outside the cell, known collectively as the extracellular matrix E!M"# There is no one matrix though, with di$$erent tissues having their own s%eci$ic E!M, which may &e dynamic or static in structure# 'n %articular the E!M has signi$icant roles in normal tissue develo%ment, $unction and disease# This matrix is manu$actured &y cells, secreted and modi$ied outside the cell &y several di$$erent enzymes (istory related to cell )unctions research $inding*+,- .asal lamina instructs innervation /oshua Sanes and /ack McMahan show that regenerating nerve axons take their cues $or new syna%se $ormation $rom the extracellular matrix E!M" o$ muscle cells and not $rom the muscle cells themselvesThis $irst lecture introduces the E!M and descri&es the ma)or $i&er $i&re" and matrix com%onents, the second lecture will cover the ma)or E!M glyco%roteins and ex%erimental studies o$ E!M $unction# E!M Function 0Su%%ort $or cells 01attern o$ E!M regulates 2%olarity 2cell division 2adhesion 2motility 03evelo%ment 2migration 2di$$erentiation 2growth $actors E!M Features 0sta&le and a&le to &e reorganised 0di$$erent $or di$$erent tissues HOW THE EXTRACELLULAR MATRIX COULD, IN PRINCIPLE, PROPAGATE ORDER FROM CELL TO CELL WITHIN A TISSUEFor sim%licity, the $igure re%resents a hy%othetical scheme in which one cell in$luences the orientation o$ its neigh&oring cells# 't is more likely, however, that the cells would mutually a$$ect one another4s orientation#E!M Structure 05lyco%roteins 0Fi&ers 2!ollagen2 main $i&ers 2Elastin 0(ydrated Matrix 21roteoglycans 2high car&ohydrate 06dhesive 27aminin 2Fi&ronectin Sha%es and Sizes E!M molecules THE COMPARATIVE SHAPES AND SIZES OF SOME OF THE MAJOR EXTRACELLULAR MATRIX MACROMOLECULESProtein is so!n in green, "n# $%&'os"(ino$%&'"n in red. !ollagen 0tensile strength and elasticity 2Tendons 2!artilage 2.one 0hal$ total &ody %roteins &y weight" !ollagen !om%onents 0'nsolu&le glyco%rotein 0%rotein 8 car&ohydrate 21rotein )high glycine )high %roline )hydroxylysine )hydroxy%roline )gly292:"n 2!ar&ohydrate )glucose )galactose !ollagen Structure !ollagen 1rotein ); %oly%e%tide a" chains )le$t hand helix, $orms $i&ers )many di$$erent verte&rate" collagens &y di$$erent com&inations o$ a2chains )Ty%e ', '', ''' main $i&ers, $lexi&le )Ty%e ' &one, skin, tendons +N to >> k3a com%osed o$ the amino acids glycine, valine, alanine, and %roline cross2linked tro%oelastin monomers $irst secreted as solu&le %recursors tro%oelastin" assem&ly and crosslinking o$ tro%oelastin monomers $orm insolu&le elastin matrix into $unctional $i&res lysine residues in the cross2linking domain o$ secreted tro%oelastin ra%idly cross2linked &oth inter2 and intra2molecularly &y lysyl oxidase" hydro%ho&ic segments 2 elastic %ro%erties B2helical segments alanine2 and lysine2rich" 2 $orm cross2links &etween ad)acent molecules Elastin Structureelastic $i&er synthesisElastin Functionstructural integrity and $unction o$ tissues reOuiring reversi&le extensi&ility or de$orma&ility high levels in tissues that reOuire elasticity lung, skin, ma)or &lood vessels Elastin 3isordersWilliams Syndrome hyaluronan2&inding %roteins 1roteoglycans consist o$ %rotein PM=" and %olysaccharide chain P+M=" $orm a gel to em&ed the $i&ril network 5olgi a%%aratus 2 565 disaccharides are added to %rotein cores to $orm %roteoglycans *Q!, and $ixed and stained while still $rozen a %rocess called $reeze su&stitution" to %revent the GAG chains $rom colla%sing# 'n this e%e'tron (i'ro$r"-, the -roteo$%&'"n (o%e'0%es are seen to $orm a $ine $ilamentous network in which a single striated 'o%%"$en +i,ri% is em&edded# The more darkly stained %arts o$ the -roteo$%&'"n (o%e'0%es are the core -roteinsH the $aintly stained threads are the GAG chains# Ie%roduced $rom E#.# (unziker and I#R# Schenk, J. Cell Biol. +-GC,,SC-C, *+-M# T The Iocke$eller Kniversity 1ress#"5lycosaminoglycans 5ags"Five ty%es (yaluronan or hyaluronic acid" main glycosaminoglycan in connective tissue high molecular weight P MW *, #"&s/ +e! in+%"(("tor& 'e%%sAInter(e#i"te !o0n# e"%in$ e2entsMesen'&("% 'e%% 'e(ot"8is "n# -ro%i+er"tionAn$io$enesisE-ite%is"tion ?/< #"&s "+ter inG0r&Me#i"te# ,& '&to1inesIntermediate wound healing eventsMesen'&("% 'e%% 'e(ot"8is "n# -ro%i+er"tionFi,ro,%"sts/ (i$r"tion "n# -ro%i+er"tionS(oot (0s'%eAn$io$enesis/ re'onstr0'tion o+ 2"s'0%"t0reSti(0%"teJ Hi$ %"'t"te, "'i#i' P, %o! O? tensionEn#ote%i"% 'e%% (i$r"tion "n# -ro%i+er"tionIntermediate wound healing eventsE-ite%is"tionP"rti"% ti'1ness/ Ce%%s #eri2e# +ro( !o0n# e#$es "n# e-ite%i"% "--en#"$esAIn'ision"% !o0n#J 'e%%0%"r (i$r"tion o2er %ess ten 5 ((A Wo0n# se"%e# in ?