Structure&FunctionsofCellMembraneDr.AnWeiDepartmentofCellBiologyCapitalMedicalUniversity

(anwei@)Cellmembrane(CM):Cellisseparatedbyathin,fragilestructure,calledcellularplasmamembrane,whichisonly50-10nminwide.Likelytobeaunitmembrane:sandwich,tri-plateformat,dark-light-darkCMcytosolStructureofcellmembraneundertheEMBiomembraneCellmembrane:exteriormembranecoveredonsurfaceofcell

Internalmembrane：alltheendomembranerelatedtoorganellswithincellOverviewofmajorcomponentsofeukaryoticcellarchitectureOverton’smembranestructurePermeabilityisinfluencedbyso-calledmembrane？HigherinlipiddissolvingMembraneiscomposedoflipid？ErnstOverton,UniversityofZurichfirstdescribedthepermeabilityofplantcellsin1890s,LowerinlipiddissolvingPermeabilityisincreasedwithitssolubilitywithinlipidIn1925,E.GorterandF.Grendelreasonedthatcellmembranesmustbeaphospholipidbilayer,twomoleculesthick.DiscoveryoflipidbilayerinRBCbyE.Gorter&F.GrendelH2OH2OPhenomenon:IfmembraneofRBCisplatedonwatersurfaceareaoflipidRBCsurfacingResult:Theratioofsurfaceareaofwatercoveredbytheextractedlipidalwaysvariedbetween1.8~2.2:1.0(or2).≈2Conclusion:plasmamembranecontainedmolecularlayeroflipids,lipidbilayer.ExistenceofproteininmembraneH2Otension>>Phenomenon:surfacetensionoflipidbilayerofRBCismuchlessthe“Purelipidstructure”Conclusion:lipidlayerismixedbyothersubstance?tension=Lipidbi-layerofRBCPurelipidstructure(liposome)Phenomenon:IfsomeproteinsareaddedintothesolutionResults:Twolayershaveanidenticaltension.proteinHypothesisofSandwichModel蛋白質(zhì)通道Interior“protein--lipid--protein”ExteriorLipidPuzzlesraisedfromSandwichModelMembranethickness5nmIfmembraneisthoroughly6-7nminthickness,inwhichlipidistaken5nm,thentherestshouldbe1-2nminthickness.Onlyproteinwithb-sheetstructurehassuchthicknessstructure,however,membraneproteinsareactuallyahelixinformat.Conclusion:

lipidsincellmembraneprobablyarenotcoatedbyprotein.6-7nm1-2nmLipasedigestionlipaseIflipidincellmembraneiscoatedbyalayerofprotein,itcannotbedigestedbylipaseanymore.

Infact,itcanbewelldissolvedbylipase.RatiobetweenlipidandproteinQuestion:

Sandwichmodelemphasized

ratiobetweenlipidandprotein.

Iffact:

inmitochondrialmembrane,theratiobetweenproteinandlipidis3.2;whilein(protein/lipid0.23)mylinmitochondria1.CMismadeupoffluidiclipidbi-layersandisentityoflipidsandproteins2.Proteinsareembeddedinlipidbi-layerbyavarietyofformsLipidbi-layerpolarheadHydrophobictailPeripheralproteinIntegralproteinThebestexplanationtostructureofcellmembranefluidmosaicmodel(proposedbyJSinger&GNicolsonofUCSD)polysaccharidesAmembraneisamosaicofdifferentproteinsembeddedanddispersedinthephospholipidbilayer.Theseproteinsvaryinbothstructureandfunction,andtheyoccurintwospatialarrangements:1-Integralproteins2-PeripheralproteinsChemicalcompositionofCMCMiscomposedofLipids:50%Proteins:40%Carbohydrate:1-10%H2O,inorganicsalts:variedmembranelipid：includesalltypesoflipidonthecellmembranephospholipidsglycolipidcholesterolMembranelipidTheyaremainly:ConformationandcategoriesTakeupto5％。About40typesComposition：

Sugarandsugarchainexample：

ABObloodtypeFunction：

RecognitionSignaltransduction；Membraneglycolipids---theirconformationandCategoriesBloodtypearedeterminedbyglycolipidN-乙酰半乳糖胺轉(zhuǎn)移酶半乳糖胺轉(zhuǎn)移酶Mother/Father

OABABOOO,AO,BABAO,AO,AO,A,B,ABA,B,ABBO,BO,A,B,ABO,BA,B,ABABA,BA,B,ABA,B,ABA,B,ABTay-SachsDiseaseiscausedbyadefectinoneenzyme(HexosaminidaseA)catalyzingastepinthelysosomalbreakdownofganglioside.Theresultingaccumulationoftheseglycolipids,especiallyinnervecell,hasdevastatingconsequences.Thesymptomsofthisdiseaseareusuallyevidentbeforeageof1.Affectedchildrencommonlybecomedementedandblindbyage2anddiebeforetheirthirdbirthday.GalNAcGalGluCeramideSiAGangliosideFindingsinretina“cherryredspot”American

neurologist

BernardSachsBritish

ophthalmologist

WarrenTay

BernardSachsTay-Sachsdiseasecurrentlyhasnotreatment,nocure,andisfatalinchildrenDakotaisan9-yearoldfromOlmstedFalls,Ohiothatisbattlingthishereditary,degenerativeneurologicaldisease.DakotaunderwentacordbloodtransplantatDukeMedicalCenterinJanuaryof2006,butthediseasecontinuestoprogress.

Sheisslowlylosinghermentalandphysicalcapabilitiesbecauseherbodyismissingavitalenzymeneededtoclearwastefrombraincells.Oneinevery250peoplecarriesthisfatalgenemutationthatispassedontoachildwhentwocarrierparentspassthegenetotheirbaby.Thecarrierratesincreaseto1in27intheAshkenaziJewish,LouisianaCajun,andFrenchCanadianpopulations.TheIrishAmericanpopulationfinds1inevery50peopletobecarriersoftheTay-Sachsgene.Atherosclerosisisadiseaseaffectingarterial

bloodvessels.Itisachronicinflammatoryresponseinthewallsofarteries,inlargepartduetotheaccumulationofmacrophage

cellsandpromotedbylowdensity(especiallysmallparticle)lipoproteins(plasmaproteinsthatcarrycholesterolandtriglycerides)withoutadequateremovaloffatsandcholesterolfromthemacrophagesbyfunctionalhighdensitylipoproteins(HDL).Severeatherosclerosisoftheaorta.Autopsyspecimen.Notethefourringstructurecommontoallsterols.SterolcanbeusedashormoneSterolsAsHormones“Designersteroids”aremajorsportingnewswheretheyhavebeenusedillegallyintrackandfield,baseball,footballandcountlessothersports.AheavilymuscledLinfordChristiewhowasdisqualifiedfrominternationalcompetitionaftertestingpositiveforabannedsteroid.VariationoflipidsindifferenttypesofcellinmammalsFigure10-16MolecularBiologyoftheCell(?GarlandScience2008)Lipidrapftmodel(脂筏模型）PCandSP=1:1PC:SP:Cholesterol=1:1:1Figure10-14bMolecularBiologyoftheCell(?GarlandScience2008)LipidsinthecellMembranearemoveableQuantificationoflateralmovementofproteinandlipidwiththeplasmamembraneLipidbi-layerislocatedbetweenthewaterAfewtypesoflipidfluidityareavailableFigure10-11bMolecularBiologyoftheCell(?GarlandScience2008)1.側(cè)向擴(kuò)散(Bilateral)2.旋轉(zhuǎn)Rotation3.擺動(dòng)Swing4.翻轉(zhuǎn)(Flip)TypesoflipidmovementsDANAMICNATUREOFMOLECULESINTHEMEMBRANEHeatincrease(一)LipidsaremovableMembranefluidityisinfluencedbytemperatureandbyitsconstituents.Astemperaturescool,membranesswitchfromafluidstatetoasolidstateasthephospholipidsaremorecloselypacked.Membranesrichinunsaturatedfattyacidsaremorefluidthatthose

dominatedbysaturated

fattyacidsbecausethe

kinksintheunsaturated

fattyacidtailsprevent

tightpacking.1.脂肪酸鏈的飽和程度:飽和高---流動(dòng)性差,Tm2.脂肪酸鏈的長度：越長，流動(dòng)性越差3.膽固醇的影響：含量高，流動(dòng)性越差4.卵磷脂/鞘磷脂的比例:比例高，流動(dòng)快5.其它因素FactorscontrollingthelipidmovementsSaturationoffattyacidLengthoffattyacidContentratiooffattyacidCholine-containingphsophlipidratiooffattyacidOtherfactorsIncludesalltheproteinsassociatedwithCM1、Dualityinpolarity,

hydrophobicandhydrophilic；2、hydropholicregionisexposedtosurfaceofCMandiscapabletobindwithwater3、hydropholicregionislocatedinsidetheCMandresistanttobindingwithwater4、hardtobeextractedandpurifiedFeatures：MembraneProteinclassifications

Extrinsic(peripheral)proteinsIntrinsic(integral)proteinsMembraneproteinsAtbothsidesofCMWatersoluableBoundwithCMbyionicbondPurificationwithionicsolutionIntegrated,transmembraneDualinpolarityBindtightlywithmembraneDiagramofvariousproteinsassociatedwithlipidbilayerMembraneProteinsFunctionalclassification(1)TransmembraneProteinsMembraneProteinsFunctionalclassification(2)TransmembraneProteinsGlycophorinA,atypicalsingle-passtransmembraneproteinStructuralmodelofbacteriorhodospin,amulti-passtransmembraneproteinTwoswitchdomainshavebeenidentified,thatchangepositionwhenGTPsubstitutesforGDPonGa.MembraneProteinsFunctionalclassification(3)PeripheralProteins(onlyonesideofthemembrane)protein：a-sheetCMCytosollipidsMolecularCharacteristicsoflipdsandproteinsinthemembraneKeyfeaturesofmembranemolecules:AsymmetrymobilityFirstly,compositionsoflipidsvaryineachlayerCellMembraneNon-cytolic：Phhosphodcholinearemostlylocatedinexteriors）cytosol：Phosphatidyl-serineorethnolamineareoftenfoundincytosolicsides.Secondly,glycolipidsareuniquefoundinout-leaflet(outside)of CMAsymmetryoflipidbilayers1.Theredistinctorientationoftransmembraneproteins2.GlycoproteinsarealwaysfoundinexteriorofcytosolAsymmetryofmembraneproteinsMovementsofmembraneproteinsMousecell小鼠細(xì)胞MembraneproteinlabeledbyAnti-humanAbHeterokaryoticcell異核細(xì)胞Antimouse-surfaceAb+fluroesinBAntihuman-surfaceAb+flue