細(xì)胞連接、細(xì)胞粘附與細(xì)胞外基質(zhì)細(xì)胞生物學(xué)課件208

第八章細(xì)胞連接、細(xì)胞粘附與細(xì)胞外基質(zhì)人體和其他多細(xì)胞生物都由細(xì)胞按特定方式有序構(gòu)建細(xì)胞連接

（celljunction）

機(jī)體大多數(shù)組織的細(xì)胞通過細(xì)胞與細(xì)胞間的連接結(jié)合在一起。具有多種類型和多種作用。細(xì)胞外基質(zhì)（extracellularmatrix

）

填充細(xì)胞間隙，形成支撐框架提供細(xì)胞生存和行為的環(huán)境

人體和其他多細(xì)胞生物都由細(xì)胞按特定方式有序構(gòu)建Connectivetissueandepithlialtissuerepresenttwoextremesoforganization.第一節(jié)細(xì)胞連接細(xì)胞連接（celljunction）的概念多細(xì)胞生物中細(xì)胞與細(xì)胞之間、細(xì)胞與細(xì)胞外基質(zhì)之間的一些特化的連接裝置對機(jī)體的構(gòu)建和功能非常重要功能性分類結(jié)構(gòu)性分類封閉連接緊密連接隔狀連接僅見于無脊椎動(dòng)物錨定連接粘合帶粘合斑橋粒半橋粒連接細(xì)胞與細(xì)胞連接細(xì)胞與細(xì)胞外基質(zhì)連接細(xì)胞與細(xì)胞連接細(xì)胞與細(xì)胞外基質(zhì)通訊連接間隙連接化學(xué)突觸胞間連絲僅見于植物細(xì)胞Celljunctionscanbeclassifiedintothreefunctionalgroups一、封閉連接（occludingjunctions)tightjunction（緊密連接）septatejunctions

Sealcellstogetherinanepitheliuminawaythatpreventevensmallmoleculesfromleakingfromonesideofthesheettotheother.上皮細(xì)胞間的緊密連接相鄰細(xì)胞質(zhì)膜上的封閉索Sealingstrand緊密連接中的跨膜蛋白密封蛋白封閉蛋白跨膜蛋白：封閉蛋白（claudin）密封蛋白（occludin）ZO蛋白EachtightjunctionsealingstrandiscomposedofalongrowoftransmembraneadhesionproteinsoccludingjunctionsformaselectivepermeabilitybarrieracrossepithelialcellsheetsTheirpermeabilitytosmallmoleculesvarygreatlyindifferentepithelia.ThesedifferencesreflectdifferencesintightjunctionproteinsthatformthejunctionsTranscellulartransportBarrierstothedifussionofsomemembraneproteins密封蛋白封閉蛋白Theclaudinsarethemaincomponentsofthesealingstrands.Theyfunctionanddifferindifferenttightjunctions.Thefunctionoftheoccludinsisuncertain.Severalotherproteinscanbefoundassociatedwiththightjunctions.位置形態(tài)和結(jié)構(gòu)作用

緊密連接（tightjunction）二、錨定連接（anchoringjunction）Mechanicallyattachcells(andtheircytoskeletons)totheirneighborsortotheextracellularmatrix.將一個(gè)細(xì)胞的骨架成分與相鄰細(xì)胞的骨架成分、或與細(xì)胞外基質(zhì)錨定在一起的結(jié)構(gòu)廣泛分布于動(dòng)物的各種組織內(nèi)，在上皮、肌肉、心臟等需要承受機(jī)械壓力的組織中尤為豐富。二、錨定連接（anchoringjunction）Anchoringjunctionsarecomposedoftwomainclassesofproteins:細(xì)胞內(nèi)錨定蛋白（與骨架附著）跨膜黏附蛋白（黏附分子）錨定連接類型（根據(jù)連接的細(xì)胞骨架成分不同）3.橋粒（desmosome）4.半橋粒（hemidesmosome）1.黏合連接（adherensjunctions）2.黏合斑（Focaladhesions）與微絲相連與中間絲相連微棘褶皺收縮環(huán)Actinfilamentsareoftennucleatedattheplasmamembrane微絲的成核作用通常發(fā)生在質(zhì)膜的下方ERM蛋白可以幫助將微絲附著到質(zhì)膜上Adherensjunctionsconnectbundlesofactinfilamentsfromcelltocell.Inepitheliatheyoftenformacontinuousadhesionbelt(黏合帶).位于上皮細(xì)胞頂部側(cè)面，緊密連接下方，是細(xì)胞與細(xì)胞之間的帶狀黏合，對形態(tài)發(fā)生起重要作用。 Adherensjunctionsareformedbytransmembraneadhesionthatbelongtothecadherin(鈣黏素)family.Theactinisattachedtomembranethroughasetofintracellularanchorproteins(catenins、vinculin、-actinin)Thistranscellularnetworkcancontractwiththehelpofmyosinmotorproteins,anditisthoughttohelpthefoldingofepithelialcellsheetintotubesandotherrelatedstructures.Theassemblyoftightjunctionsbetweenepithelialcellsseemstorequirethepriorformationofadherensjunctions.黏合帶（adhesionbelt）位置：位于上皮細(xì)胞頂部側(cè)面、緊密連接的下方形態(tài)和結(jié)構(gòu)：是連續(xù)的帶狀粘附連接蛋白成分：細(xì)胞內(nèi)錨定蛋白包括連環(huán)蛋白、紐蛋白和α-輔肌動(dòng)蛋白等，跨膜粘附蛋白為鈣粘素作用：在早期胚胎中使上皮細(xì)胞片層內(nèi)陷形成管狀器官原基，對形態(tài)發(fā)生起重要作用胞內(nèi)錨定蛋白：連環(huán)蛋白（catenin）紐蛋白（vinculin）

α-輔肌動(dòng)蛋白(α-actinin)跨膜黏附蛋白：

鈣黏素（cadherin）黏合帶（adhesionbelt）管腔和腺體上皮細(xì)胞側(cè)壁，鈕扣或鉚釘狀連接相鄰細(xì)胞橋粒（desmosome）Desmosomeconnectintermediatefilamentsfromcelltocell.胞內(nèi)錨定蛋白：橋粒珠蛋白（plakoglobin）橋粒斑蛋白（desmoplakin）跨膜黏附蛋白：橋粒芯糖蛋白（desmoglein）橋粒芯膠蛋白（desmocollin）組成橋粒的一些分子橋粒斑蛋白橋粒珠蛋白橋粒芯膠蛋白橋粒芯糖蛋白細(xì)胞內(nèi)錨定蛋白：Amixtureofintracellularanchorproteinscomposeadenseplaqueonthecytoplasmicsurfaceofeachinteractingplasmamembrane.Transmembraneadhesionproteins(desmogleinanddesmocollin)aremembersofthecadherinfamily.Theparticulartypeintermediatefilamentsattachedtothedesmosomesdepensonthecelltype.橋粒（desmosome）位置：

管腔和腺體上皮細(xì)胞側(cè)壁

相鄰細(xì)胞接觸點(diǎn)上一種類似鈕扣的點(diǎn)狀細(xì)胞連接，能牢固地將相鄰細(xì)胞扣在一起形態(tài)：

鈕扣或鉚釘狀連接相鄰細(xì)胞，但保持細(xì)胞間隙蛋白成分:胞內(nèi)錨定蛋白；跨膜黏附蛋白(鈣黏素）作用：維持上皮組織結(jié)構(gòu)細(xì)胞質(zhì)骨架(中間絲)與疾病Skindiseases--角蛋白基因突變:單純性大泡性表皮松懈癥Anchoringjunctionsformedbyintegrinsbindcellstotheextracellularmatrix:Focaladhesions（黏合斑）Hemidesmosome（半橋粒）Focaladhesionsenablecellstogetaholdontheextracelularmatrixthroughintegrinsthatlinkintracellularlytoactinfilaments.Focaladhesions細(xì)胞通過局部粘附與細(xì)胞外基質(zhì)之間形成的粘合連接跨膜粘附蛋白為整合素，介導(dǎo)胞外與細(xì)胞外基質(zhì)成分相連錨定蛋白包括距蛋白、α-輔肌動(dòng)蛋白、細(xì)絲蛋白和紐蛋白等，胞內(nèi)通過錨定蛋白與微絲相連

Hemidesmosome,orhalf-desmosom,resembledesmosomemorphologicallyandinconnectingtointermediatefilaments胞內(nèi)錨定蛋白：網(wǎng)蛋白（plectin）跨膜黏附蛋白：整合素（integrin）半橋粒（hemidesmosome）位置:上皮細(xì)胞與細(xì)胞外基質(zhì)接觸點(diǎn)(一種點(diǎn)狀細(xì)胞連接)形態(tài):鉚釘狀連接上皮基底面與基膜，只有橋粒的一半結(jié)構(gòu)，其致密斑只存于上皮細(xì)胞的胞質(zhì)面蛋白成分:胞內(nèi)錨定蛋白,網(wǎng)蛋白;跨膜黏附蛋白,整合素作用:使上皮組織固定，并分散所承受的機(jī)械張力

錨定連接類型3.橋粒（desmosome）4.半橋粒（hemidesmosome）1.黏合連接（adherensjunctions）2.點(diǎn)狀黏合（Focaladhesions）三、通訊連接（communicatingjunction）存在于大多數(shù)組織中相鄰細(xì)胞膜上的特殊連接通道實(shí)現(xiàn)細(xì)胞間電信號和化學(xué)信號的通訊聯(lián)系完成群體細(xì)胞間的合作和協(xié)調(diào)包括：間隙連接、化學(xué)突觸、胞間連絲1.間隙連接（gapjunction）又稱縫隙連接gapjunction(間隙連接)allowsmallmolecules(suchasinorganicions,sugars,aminoacid,nucleotides,vitamins,cAMP)topassdirectlyfromcelltocell.Channel-formingproteins(connexins)間隙連接通透的物質(zhì)或離子有一定的大小限制Amaximalfunctionalporesizefortheconnectingchannelsisabout1.5nm.連接子（connexon）Agap-junctionconnexonismadeupofsixtransmembraneconnexinsubunits.Connexinsarefour-passtransmembraneproteins.Mostcelltypeexpressmorethanonetypeofconnexins.Twodifferentconnexinproteinscanassembleintoaheteromeric

connexon.Adjacentcellsexpressingdifferentconnexinscanformintracellularchannelsinwhichthetwoalignedhalf-channelsaredifferent.ThemRNAinjectionapproachhasbeenusefulforidentifyingnewgap-junctionproteinseg.ShakingBFrogoocytesGap-junctionshavediversefunctions.Thepermeabilityofgap-junctionscanberegulatedconnexins.間隙連接（gapjunction）存在于

動(dòng)物細(xì)胞（少數(shù)終末分化細(xì)胞除外）體外培養(yǎng)細(xì)胞呈斑塊狀，由成簇的連接子組成電化學(xué)和代謝上偶聯(lián)兩個(gè)細(xì)胞相鄰質(zhì)膜上的跨膜蛋白分子形成連通的通道

——連接子（connexon）。每一個(gè)縫隙連接都含有一簇連接子，數(shù)量可達(dá)數(shù)百。連接子是由6個(gè)連接蛋白亞單位構(gòu)成。間隙連接（gapjunction）作用和特點(diǎn)介導(dǎo)細(xì)胞間電的偶聯(lián)和化學(xué)的偶聯(lián)。通透的物質(zhì)或離子有一定的大小限制。有組織特異性（連接蛋白不同、通透性不同）。通透性是可調(diào)的。間隙連接（gapjunction）2.化學(xué)突觸（chemicalsynapse）存在于神經(jīng)細(xì)胞間和神經(jīng)細(xì)胞與肌細(xì)胞間的接觸部位?；瘜W(xué)突觸的質(zhì)膜間有20nm的突觸間隙。信號傳遞速度較慢，電信號→化學(xué)信號→電信號。3.胞間連絲（plasmodesmata）是植物細(xì)胞間的通訊連接相鄰細(xì)胞的質(zhì)膜形成圓柱形胞質(zhì)通道

分子量小于800Da的物質(zhì)通過信號傳遞速度較慢，電信號→化學(xué)信號→電信號在植物細(xì)胞間的物質(zhì)運(yùn)輸和細(xì)胞通訊中起重作用胞間連絲示意圖封閉連接錨定連接通訊連接細(xì)胞連接的類型何謂細(xì)胞黏附？細(xì)胞黏附與細(xì)胞連接又有什么不同？第二節(jié)細(xì)胞黏附概念

細(xì)胞與細(xì)胞之間、細(xì)胞與細(xì)胞外基質(zhì)之間通過一些特殊的分子彼此識別和結(jié)合是錨定連接的基礎(chǔ)，同時(shí)也在細(xì)胞的遷移和組織構(gòu)建中起重要作用。粘合帶橋粒緊密連接間隙連接半橋粒連接復(fù)合體神經(jīng)嵴細(xì)胞發(fā)生遷移集聚分化神經(jīng)細(xì)胞衛(wèi)星細(xì)胞構(gòu)成神經(jīng)節(jié)對胚胎發(fā)育中細(xì)胞的定向遷移、形成組織起重要作用細(xì)胞黏附見于上皮細(xì)胞有特化的連接區(qū)使細(xì)胞間結(jié)合牢固連接性黏附上皮的基底細(xì)胞基底細(xì)胞增殖相鄰細(xì)胞互相連接上皮擴(kuò)展細(xì)胞黏附由黏附分子介導(dǎo)細(xì)胞黏附分子（celladhesionmolecule,CAM）細(xì)胞表面跨膜蛋白包括細(xì)胞間和細(xì)胞-基質(zhì)黏附分子參與細(xì)胞間和細(xì)胞與胞外基質(zhì)的黏附有多種類型細(xì)胞黏附是選擇性的識別過程見于非上皮細(xì)胞無特化的連接區(qū)適宜細(xì)胞的運(yùn)動(dòng)非連接性黏附細(xì)胞間黏附分子結(jié)合有三種方式嗜同性結(jié)合嗜異性結(jié)合連接分子依賴性結(jié)合一、細(xì)胞黏附的基本特性1.細(xì)胞黏附由黏附分子介導(dǎo)2.細(xì)胞間黏附分子結(jié)合有三種方式3.細(xì)胞黏附的連接性黏附和非連接性黏附機(jī)制4.細(xì)胞黏附是選擇性的識別過程二、幾種主要的細(xì)胞黏附分子介導(dǎo)細(xì)胞與細(xì)胞、細(xì)胞與細(xì)胞外基質(zhì)相互粘附和作用的跨膜糖蛋白分子作為細(xì)胞粘附的分子基礎(chǔ)，參與細(xì)胞生長、發(fā)育、分化、凋亡，以及細(xì)胞識別、應(yīng)答和信號轉(zhuǎn)導(dǎo)等參與免疫應(yīng)答、炎癥反應(yīng)、組織修復(fù)、器官硬化、血栓形成、移植排斥及腫瘤轉(zhuǎn)移等多種生理、病理過程黏附分子二、幾種主要的細(xì)胞黏附分子1.鈣黏素家族2.選擇素家族3.免疫球蛋白超家族4.整合素家族1.鈣黏素家族（40多種鈣黏素）鈣黏素（cadherin）結(jié)構(gòu)：單次跨膜蛋白胞外結(jié)構(gòu)域形成重復(fù)子功能：介導(dǎo)同型細(xì)胞間的嗜同性黏附 維持細(xì)胞極性，構(gòu)建和維持組 織結(jié)構(gòu)鈣黏素重復(fù)子Calciumdependentadhesionmolecules(Cadherins)Overadozendifferenttypes.

Almostallvertebratecellsexpressoneormore

cadherins.Single-passtransmembraneglycoproteincomposedofabout700-750residues.Extracellulardomains:

containabout100aminoacidresidues

containcalciumbindingsites

bindinahomophilicpatternCa2+對鈣黏素的影響細(xì)胞間的嗜同性黏附鈣黏素——Ca2+依賴的黏附分子鈣黏素的嗜同性黏附在胚胎發(fā)育不同階段的細(xì)胞識別、遷移和分化以及組織器官的構(gòu)建和修復(fù)中起重要作用。連環(huán)蛋白聯(lián)結(jié)蛋白輔肌動(dòng)蛋白經(jīng)典鈣黏素通過錨定蛋白與微絲結(jié)合WellknowntypesofCalciumdependentadhesionmolecules:TypeofCadherinWhattissues?Structure:IntracellularbindingproteinsCytoplasmic

filamentsE-Cadherin;

P-Cadherinepithelialcellsadhesionbeltscatenins,

-actininactinDesmosomalCadherinepidermisandplacentadesmosomesdesmoplakinsI,II;Plakoglobinkeratin;desmin

N-Cadherinnerve,muscle,lenscellsadhesionbeltscatenins,-actinin,vinculinactin2.選擇素家族結(jié)構(gòu)：單次跨膜蛋白高度糖基化重要活性部位：凝集素結(jié)構(gòu)域功能：介導(dǎo)白細(xì)胞與血管內(nèi)皮細(xì)胞或血小板的識別和黏附 啟動(dòng)炎癥免疫反應(yīng)及維持炎癥狀態(tài)凝集素結(jié)構(gòu)域選擇素（selectin）依賴Ca2+的黏附分子CelltoCellSurfaceCarbohydrateBindingProteins(Selectins)*Transienttransmembranebindingproteins(lectins)

*InthepresenceofCalcium,bindtospecific

oligosaccharidesonanothercell

*"Heterophilic"celladhesion(bindingproteinbindstoanothertypeofsiteonacell

選擇素與整合素介導(dǎo)白細(xì)胞遷移3.免疫球蛋白超家族（immunoglobinsuperfamily）不依賴Ca2+的黏附分子神經(jīng)細(xì)胞黏附分子免疫球蛋白樣結(jié)構(gòu)域常與鈣黏素共表達(dá)免疫球蛋白超家族（immunoglobin

superfamily）成分ICAM、VCAM、NCAM等

結(jié)構(gòu)不依賴Ca2+的黏附分子胞外區(qū)有一個(gè)或多個(gè)Ig樣結(jié)構(gòu)域

分布

淋巴細(xì)胞、單核細(xì)胞、內(nèi)皮細(xì)胞、上皮細(xì)胞功能與整合素介導(dǎo)白細(xì)胞與內(nèi)皮細(xì)胞牢固粘附參與免疫炎癥反應(yīng)整合素（integrin）又稱整聯(lián)蛋白跨膜異二聚體糖蛋白（αβ），種類繁多，人體：24種α，9種β分布淋巴細(xì)胞、單核細(xì)胞、中性粒細(xì)胞、血小板功能是多數(shù)細(xì)胞外基質(zhì)成分的細(xì)胞表面受體

介導(dǎo)細(xì)胞間或細(xì)胞與胞外基質(zhì)間黏附，參與信號傳導(dǎo)，調(diào)控細(xì)胞功能4.整合素家族*Integrinsaretransmembraneheterodimers*IntegrinsmustinteractwiththecytoskeletontobindcellstotheECM*Cellscanregulatetheactivityoftheirintegrins*Integrinsactivateintracellularsignalingpathways整合素參與黏合斑形成整合素介導(dǎo)細(xì)胞骨架與細(xì)胞外基質(zhì)的聯(lián)系整合素介導(dǎo)的由內(nèi)向外的信號轉(zhuǎn)導(dǎo)途徑整合素配體胞內(nèi)信號級聯(lián)反應(yīng)2.細(xì)胞通過表面特異受體與細(xì)胞外基質(zhì)成分結(jié)合如血小板被信號分子激活機(jī)體組織由細(xì)胞和細(xì)胞外基質(zhì)構(gòu)成何為細(xì)胞外基質(zhì)呢？形態(tài)、結(jié)構(gòu)分子組成與細(xì)胞的關(guān)系所起的作用或所具有的功能第三節(jié)細(xì)胞外基質(zhì)概念由細(xì)胞分泌的多種大分子組成的復(fù)雜網(wǎng)絡(luò)結(jié)構(gòu)，充滿著細(xì)胞之間的大小間隙功能：形成一種支撐性框架，為細(xì)胞提供一種有組織的外環(huán)境。Inanimals,theextracellularmatrix:*helpsorganizecellsintotissues*coordinatestheircellularfunctionsbyactivatingintracellularsignalingpathwaythatcontrolcellgrowth,proliferation,andgeneexpression.ExtracellularMatrix(ECM）：TheECMisanorganizednetworkofcollagens,proteoglycansand

glycoproteins.Inadditiontoprovidinganexternalscaffoldthatcellsattachto,theECMinfluencesthedevelopmentandbehaviorof

cells.SpecializedECMstructures,calledthebasementmembraneor

basallamina,underlieallepithelialcellsheetsandtubesandsurroundbloodvessels.Ⅰ.ExtracellularMatrix(ECM）

在不同組織中細(xì)胞外基質(zhì)成分、含量和存在形式的差異

基質(zhì)鈣化大量成索的膠原纖維特化為基膜

骨組織堅(jiān)硬肌腱、韌帶具有強(qiáng)大的張力控制細(xì)胞的行為TheECMiscomposedof3majorclassesofbiomolecules:

Structuralproteins:collagenandelastin.(膠原、彈性蛋白)2.

Specializedproteins:

e.g.fibrillin

（原纖蛋白）,fibronectin（纖黏連蛋白）,andlaminin（層黏連蛋白）.3.

Proteoglycans（蛋白聚糖）:thesearecomposedofaproteincoretowhichisattachedlongchainsofrepeatingdisaccharideunitstermedofglycosaminoglycans(糖胺聚糖，GAGs)formingextremelycomplexhighmolecularweightcomponentsoftheECM.這些胞外基質(zhì)中的大分子各自起著什么樣的作用？1.膠原（collagen）Mostabundantanimalprotein(30%total)Hydroxylysineandhydroxyproline(25%ofAA),glycine(30%)Collagenscanfoldandcross-linkintofibrilsandnetworks20differentcollagengenesover7chromosomes女性皮膚為何老得快？

中新網(wǎng)10月10日電據(jù)生命時(shí)報(bào)報(bào)道，雖然女性花在護(hù)膚上的金錢和時(shí)間遠(yuǎn)多于男性，但她們似乎仍難以抗拒自然的力量。德國研究人員最近發(fā)現(xiàn)，女性皮膚的衰老速度要比男性快，研究還發(fā)現(xiàn)，膠原蛋白流失是皮膚衰的老主要原因。

膠原蛋白和彈性蛋白是皮膚中的兩種蛋白質(zhì)，皮膚的生長、修復(fù)、營養(yǎng)以及彈性、張力等都與它們有著密切聯(lián)系。其中膠原蛋白的作用更加重要，75%的真皮層由膠原蛋白組成，它們擔(dān)負(fù)著抗皺與保濕兩大關(guān)鍵使命。人體在年輕時(shí)能夠制造許多膠原蛋白，但它們的產(chǎn)量會隨著年齡增長而減少。ThecollagentriplehelixViewdowntheaxisofthetriplehelixRepeatsetsofthreea.a,Gly-X-YProcollagenisproducedinthesecretorysystem.

Collagenfibersareassembledextracellularly.膠原分子前膠原膠原原纖維膠原纖維膠原纖維膠原纖維的形成過程膠原原纖維膠原類型：原纖維形成膠原:I、II、III、V網(wǎng)絡(luò)形成膠原：IV、VII原纖維相關(guān)膠原：VI、IXThereareatleast12typesofcollagen各種組織中膠原成分有所不同膠原原纖維在不同組織中排列方式不同各種組織中膠原成分有所不同皮膚和骨組織以I型膠原為主軟骨組織以II型膠原為主要成分基膜以IV型膠原為主要成分膠原原纖維在不同組織中排列方式不同皮膚中

呈交織狀排列抵抗不同方向的張力肌腱中

呈平行的條索狀排列與張力的主軸方向平行骨和角膜中

呈膠合板樣成層排列Interactionsoffibrouscollagenswithnonfibrousfibril-associatedcollagens.IntendonsIncartilageCollagenTypeIVformsthemeshworkofbasementmembranes(basallamina).可高度拉伸的皮膚“彈性皮膚人”JamesMorris異?？衫斓钠つw是一種遺傳綜合征的表現(xiàn)，由于膠原蛋白組裝或交聯(lián)中的缺陷所致。彈性蛋白分子網(wǎng)絡(luò)的伸展和回縮2.彈性蛋白是彈性纖維的主要成分，賦予組織彈性。在血管、皮膚中含量豐富伸展回縮彈性纖維DefinitionofElastinElastin:Aproteinthatcoilandrecoilslikeaspringwithintheelasticfibersofconnectivetissueandaccountsfortheelasticityofstructuressuchtheskin,bloodvessels,heart,lungs,intestines,tendons,andligaments.Elastinfunctionsinconnectivetissuetogetherwithcollagen.Whereaselastinprovideselasticity,collagenprovidesrigiditytoconnectivetissue.Elastinisnormallynolongermadeafterpubertyandagingbegins.彈性蛋白與膠原蛋白比較：

1.彈性蛋白沒有甘-X-Y重復(fù)順序；2.彈性蛋白不是三股肽鏈的絞合；3.彈性蛋白不含羥賴氨酸和糖。

3.纖黏連蛋白是一類非膠原糖蛋白通過整合素和跨膜黏附分子介導(dǎo)與胞內(nèi)微絲相連細(xì)胞與胞外基質(zhì)間的黏附及胞外基質(zhì)結(jié)構(gòu)的有序組建起重要作用協(xié)同序列細(xì)胞結(jié)合位點(diǎn)肝素結(jié)合位點(diǎn)Fibronectin(FN)isinvolvedinmanycellularprocesses,includingtissuerepair,embryogenesis,bloodclotting,andcellmigration/adhesion.

Fibronectin(FN)FNisRod-like,composedofthreedifferenttypesofhomologous,repeatingmodules,TypesI,II,andIII.Thesemodules,thoughallpartofthesameaminoacidchain,canbeenvisionedas"beadsonastring,"eachonejoinedtoitsneighborsbyshortlinkers.FNsometimesservesasageneralcelladhesionmoleculebyanchoringcellstocollagenorproteoglycansubstrates.FNalsocanservetoorganizecellularinteractionwiththeECMbybindingtodifferentcomponentsoftheextracellularmatrixandtomembraneboundFNreceptorsoncellsurfaces.

100nmFibronectinFibronectinsaredimersof2similarpeptides.

Fibronectin

-foundinblood,connectivetissue,andbasementmembranes.5%carbohydratebyweight.Composedof2subunitswithanaggregateMWofabout550kd.

RGDseq.=Arg-Gly-Asp.FibronectinReceptors

formafamilyofheterodimerictransmembraneproteins.collagenproteoglycanfibronectinintegrinactinfilamentLipidbilayerCellinteriorCellexterior4.層黏連蛋白是一類非膠原糖蛋白是基膜的主要成分之一，具有與胞外基質(zhì)（膠原）及細(xì)胞表面黏附分子（整合素）的結(jié)合位點(diǎn)Lamininsareheterotrimericglycoproteinsthatarecomposedofα,βandγchains.TheyareprimarilylocatedinBMs,wheretheyformnetworkswithcollagenIVandnidogen.Lamininsaffectcellularfunctionsbybindingtointegrinsandnon-integrinreceptors.

LamininStructureoflaminin5.糖胺聚糖和蛋白聚糖蛋白聚糖（1）糖胺聚糖(GAG)根據(jù)糖基組成和硫酸鹽化程度不同透明質(zhì)酸硫酸軟骨素（硫酸皮膚素）肝素/硫酸乙酰肝素硫酸角質(zhì)素GAGchainsoccupylargeamountsofspaceandformhydrategelsGAG:Mostly(-)chargedverylargeUsuallysulfatedExtended,repulsionHydratedwithlargeamountsofwaterCushionstissues,developsturgorHyaluronanisanonsulfatedGAG.Itisformedbyaplasma-membrane-boundenzyme(HAsynthase)andisspunoutdirectlyfromthecellsurfacebyanenzymecomplexembeddedintheplasmamembrane.

Insolutionitisveryflexible,bendingandtwistingintomanyconformations.Becauseofthelargenumberofanionicresiduesonitssurface,thetypicalHAbindsalargeamountsofwater.ThebindingofcationsbyCOO-groupsonthesurfaceofHAincreasestheconcentrationofionsandthustheosmoticpressure.Theseswellingforcesgiveconnectivetissuestheirabilitytoresitcompressionforces.Becauseofitsloose,hydrate,porousnature,theHAcoatboundtocellsappearstokeepcellsapartfromoneanother,giveingthemthefreedomtomoveaboutandproliferate.Thecessationofcellmovementandtheinitiationofcell-cellattachmentsarefrequentlycorrelatedwithadecreaseHA.AssociationofHAandproteoglycansformslarge,complexaggregates透明質(zhì)酸硫酸角質(zhì)素硫酸軟骨素glycoproteinDecoratesthesurfaceofcollagenAsmallandalargeproteoglycanfoundintheECMPrincipaltypesofepitheliumeg.Bloodvessels(endothelialcells)C.Linecertaincavitiessubjecttoexpansionandcontraction.eg.theurinarybladder(endothelialcells)二、基膜（basallamina）由細(xì)胞外基質(zhì)特化而成的薄層網(wǎng)絡(luò)狀結(jié)構(gòu)，厚度60-100nm位于大多數(shù)上皮細(xì)胞層和內(nèi)皮細(xì)胞層的下面，也可包繞在肌細(xì)胞、脂肪細(xì)胞和神經(jīng)鞘細(xì)胞的周圍MajorcomponentsofthebasallaminaCollagenTypeIVformsthemeshworkofbasementmembranes(basallamina).巢蛋白基底膜蛋白聚糖不同組織中基膜的結(jié)構(gòu)與功能有所不同將相鄰細(xì)胞聯(lián)系在一起，形成完整的組織（平滑肌細(xì)胞周圍）調(diào)節(jié)吸收營養(yǎng)物質(zhì)進(jìn)入血液（小腸上皮下）起者分子濾膜作用，阻止大分子通過，只讓某些小分子從血液進(jìn)入原尿（腎小球基底膜）對組織的再生和創(chuàng)傷愈合起重要作用肌肉、神經(jīng)和上皮組織損傷時(shí)

殘存的基膜可為再生細(xì)胞提供一個(gè)框架，使細(xì)胞遷入，重建原先的組織結(jié)構(gòu)皮膚或角膜損傷后

基膜的成分發(fā)生變化，如纖粘連蛋白增加，使細(xì)胞遷移至損傷部位促進(jìn)其愈合三、細(xì)胞外基質(zhì)與細(xì)胞的相互關(guān)系1.細(xì)胞控制細(xì)胞外基質(zhì)的生成和降解2.細(xì)胞通過表面特異受體與細(xì)胞外基質(zhì)成分結(jié)合3.細(xì)胞外基質(zhì)對細(xì)胞結(jié)構(gòu)與功能的影響三、細(xì)胞外基質(zhì)與細(xì)胞的相互關(guān)系1.細(xì)胞控制細(xì)胞外基質(zhì)的生成和降解細(xì)胞外基質(zhì)的成分是由細(xì)胞產(chǎn)生的，細(xì)胞外基質(zhì)成分的降解是由細(xì)胞分泌的蛋水解酶催化的三、細(xì)胞外基質(zhì)與細(xì)胞的相互關(guān)系3.細(xì)胞外基質(zhì)對細(xì)胞結(jié)構(gòu)與功能的影響（1）細(xì)胞外基質(zhì)影響細(xì)胞的形態(tài)、存活和死亡（2）細(xì)胞外基質(zhì)影響細(xì)胞的增殖和分化（3）細(xì)胞外基質(zhì)影響細(xì)胞的遷移細(xì)胞外基質(zhì)影響細(xì)胞的增殖和分化細(xì)胞只有粘附和鋪展在細(xì)胞外基質(zhì)上才能增殖一旦離開細(xì)胞外基質(zhì)變成球形時(shí)就不能增殖

外胚層細(xì)胞內(nèi)胚層細(xì)胞前羊膜腔調(diào)亡細(xì)胞基膜細(xì)胞外基質(zhì)影響細(xì)胞的形態(tài)、存活和死亡細(xì)胞的存活依賴于粘附在細(xì)胞外基質(zhì)上上皮細(xì)胞和內(nèi)皮細(xì)胞一旦脫離了細(xì)胞外基質(zhì)就會發(fā)生凋亡

ECMFunctionEndowtissueductility、elasticity、amortization.InfluencecellsurvivalanddeathDeterminecellshapeControlcellproliferationControlcelldifferentiationAffectcellmigrationPromotestraumaplerosis二、腫瘤轉(zhuǎn)移腫瘤轉(zhuǎn)移概念（WhatIsMetastasis）腫瘤轉(zhuǎn)移步驟（StepsforMetastasis）腫瘤轉(zhuǎn)移的基本過程（Stepsintheprocessofmetatasis）WhatIsMetastasis?Whenpatientsarediagnosedwithcancer,theywanttoknowwhethertheirdiseaseislocalorhasspreadtootherlocations.Cancerspreadsbymetastasis,theabilityofcancercellstopenetrateintolymphaticandbloodvessels,circulatethroughthebloodstream,andtheninvadeandgrowinnormaltissueselsewhere.Inlargemeasure,itisthisabilitytospreadtoothertissuesandorgansthatmakescancerapotentiallylife-threateningdisease,sothereisgreatinterestinunderstandingwhatmakesmetastasispossibleforacanceroustumor.Ⅱ.Tumormetastasis

StepsforMetastasisTumorcellattachmentNeovascularizationDisruptionofbasementmembraneInvasionofmalignantcellsintohoststromaIntravasationintobloodorlymphaticcirculationSurvivalandtransportExtravasationGrowthwithinnewenvironmentCarcinomainsituCancercellbecomescapableofinvasion(expressessurfaceadhesionmolecules)Tumorcellsreleaseproteolyticenzymes,disruptionofECMInvadeECMTumorcellsmetastasizebywayofbloodvesselsorlymphaticsBloodvesselLymphaticRepeatedbindingtoanddissolutionofECMStepsintheprocessofmetatasisThreestepsincrossingabasallamina-ataskthatinvasivetumorcellsmustbeabletoperformⅢ.ECMandTumorMetastasisMatrixDegration：proteomease（MMPs），polysaccharidehydrolaseAngiogenesis：cellgrowthfactor（FGF，VEGF），ECMinhibitor(Angiostatin,Endostatin,TSP)Migration：Chemokinefactor（FN，LN）Adhesion：cell—cell，cell—ECMcelladhesionmolecules:ECMreceptor—IntegrinSignaling：ECMreceptorsignaltransduction(FAK)ProteinasesFunction:Degradeextracellularmatrix(ECM),includingthebasementmembrane(BM)ImportantinnormalphysiologicalprocessesTissueremodelingandgrowthTrophoblastimplantationWoundrepairProteinases(cont.)Classes:SerineproteinasesCysteineproteinasesAsparticproteinasesMetalloproteinasesADAMs(ADisintegrinAndMetalloproteinase)MatrixMetalloproteinases

(MMPs)MMPs-familyofzinc-dependentproteasesTIMPs-tissueinhibitorsofMMPsBalancebetweenMMPsandTIMPsisstrictinnormalcells,dysregulatedinCAMMPsIncreasedinvasivecapacityTIMPSMatrixMetalloproteinase（MMPs）MatrixMetalloproteinases(MMPs）:TheMMPsareafamilyofECMdegradingenzymesthatsharescommonfunctionaldomainsandactivationmechanisms.Matrixmetalloproteinases(MMPs)constitutealargefamilyofsecretedsolubleandcell-surfacezinc-dependentendopeptidasesthatcleaveECMcomponents.Thematrixmetalloproteinases(MMPs)compriseafamilyofzinc-dependentendopeptidasesthatconsistofmorethan21humanMMPs