复旦细胞生物学课件04生物膜：结构、化学和功能

Chapter4Biomembranes:TheirStructure,ChemistryandFunctionsLearningobjectives:1.Abriefhistoryofstudiesonthestructrureoftheplasmamembrane2.Modelofmembranestructure:anexperimentalperspective3.Thechemicalcompositionofmembranes4.Characteristicsofbiomembrane5.Anoverviewofthefunctionsofbiomembranes1.AbriefhistoryofstudiesonthestructrureoftheplasmicmembraneA.Conception:Plasmamembrane(cellmembrane),Intracellularmembrane,Biomembrane.B.ThehistoryofstudyOverton(1890s):LipidnatureofPM;Toanswerthequestionthathowmanylipidlayerswereinmembrane,in1925GorterandGrendelextractedthelipidsfromaknownnumberoferythrocytesandspreadthelipidfilmonawatersurface.Theareaoflipidfilmonthewaterwasabouttwice(1.8-2.2)theestimatedtotalsurfaceareaoftheerythrocytes,sotheyconcludedthattheerythrocyteplasmamembraneconsistedofnotonebuttwolayersoflipids.GortterandGrendel(1925):ThebasisofmembranestructureisalipidbilayerCellphysiologists(1920sand1930s):ThedecreaseinsurfacetensionsofPMmightbeexplainedbytheproteins.H.DavsonandJ.Danielli(1935):“sandwichmodel”Membranesalsocontainproteins.Ifthemembranesonlyconsistofpurelipids,itcouldnotexplainallthepropertiesofmembranes.Forexample,sugars,ions,andotherhydrophilicsolutesmoveintoandoutofcellsmuchmorereadilythancouldbeexplainedbythepermeabilityofpurelipidbilayers.Toexplainsuchdifferences,DavsonandDanielliinvokedthepresenceofproteinsinmembranesin1935.Theplasmamembraneiscomposedofalipidbilayerthatislinedonbothitsinnerandoutersurfacebyalayerofglobularproteins;inadditionto,thepresenceofprotein-linedporesforpolarsolutesandionstoenterandexitthecell.J.D.Robertson(1959):TheTEMshowing:thetrilaminarappearanceofPM;Unitmembranemodel;S.J.SingerandG.Nicolson(1972):fluid-mosaicmodel;K.Simonsetal(1997):lipidraftsmodel;FunctionalraftsinCellmembranes.Nature387:569-5722.SingerandNicolson’sModelofmembranestructure:Thefluid-mosaicmodelisthe“centraldogma”ofmembranebiology.A.Thecorelipidbilayerexistsinafluidstate,capableofdynamicmovement.B.Membraneproteinsformamosaicofparticlespenetratingthelipidtovaryingdegrees.TheFluidMosaicModel,proposedin1972bySingerandNicolson,hadtwokeyfeatures,bothimpliedinitsname.3.ThechemicalcompositionofmembranesA.MembraneLipids:TheFluidPartoftheModelPhospholipids:PhosphoglycerideandsphingolipidsGlycolipidsSterols(isonlyfoundinanimals)Membranelipidsareamphipathic.Therearethreemajorclassesoflipids:ThreekindsofmovementofMembranelipidsThreekindsofmovement:Rotationaboutitslongaxis;Lateraldiffusionbyexchangingplaces;Transversediffusion,or“flip-flop”fromonemonolayertotheother.Flippasescatalyzetheflip-flop.TheeffectsoffattyacidcompositiononmembranefluidityThelengthofthefattyacidThedegreeofunsaturationoftheirsidechainsThetemperature.TheeffectsofsterolsonmembranefluidityLiposomeandapplicationStudyonnature;genetransfer;asacarrier.B.MembraneProteins:The“Mosaic”PartoftheModelMembranescontainintegral,peripheral,andlipid-anchoredproteins:Rolled-upsheethelixAmphipathichelixlipid-anchoredproteinsNoncovalentinteractionsIntegralproteinsareamphipathic,withhydrophobicdomainsanchoringtheminthebilayerandhydrophilicregionsformingfunctionaldomainsoutsideofthebilayer.Channelproteinshavehydrophiliccoresthatformaqueouschannelsinthemembrane-spanningregion.Peripheralproteinsareattachedtothemembranebyweakbondsandareeasilysolubilizad.Lipid-attachoredmembraneproteinsaredistinguishedbyboththetypesoflipidanchorandtheirorientation.ProteinscanbeseperatedbySDS-polyacrylamidegelelectrophoresisTheorientationofintegralproteinscanbedeterminedusingnonpenetratingagentsthatlabeltheproteins.Identificationoftransmembranedomainscanbepredictedfromtheaminoacidsequenceusingahydropathyplot.Membranedomainsandpolarity.Protein/lipidratiosvaryconsiderablyamongdifferentmembranetypes.Lipidandproteincomponentsofmembranesareboundtogetherbynon-covalentforces.Detergent---smallamphipathicmoleculesSDS:CH3-(CH2)11-OSO3-Na+CH3CH3CH3–C–CH2–C–(O-CH2-CH2)10-OHCH3CH3TritonX-100:Integralproteinsareembeddedinthemembrane;theirremovalrequiresdetergents.C.MembraneCarbohydratesMembranecontaincarbohydratesconvalentlylinkedtolipidsandproteinsontheextracellularsurfaceofthebilayer.Glycoproteinshaveshort,branchedcarbohydratesforinteractionswithothercellsandstructuresoutsidethecell.Glycolipidshavelargercarbohydratechainsthatmaybecell-to-cellrecognitionsites.4.CharacteristicsofbiomembraneA.DynamicnatureofbiomembraneFluidityofmembranelipid.Itgivemembranestheabilitytofuse,formnetworks,andseparatecharge;Motilityofmembraneprotein.ThelateraldiffusionofmembranelipidscandemonstratedexperimentallybyatechniquecalledFluorescenceRecoveryAfterPhotobleaching(FRAP).B.Theasymmetryofbiomembranes—ThefoundationofmembranefunctionTheasymmetryofmembranelipidsandglycolipids:Theinnerandoutermembraneleafletswereshowntohavedifferentlipidcompositions.Lipldasymmentrygivesthemembraneleafletsdifferentphysicalandchemicalpropertiesappropriateforthedifferentinteractionsoccurringatthetwomembranefaces.TheasymmetricdistributionofPLinHETheasymmetryofmembraneproteinandglycoprotein:Integralpr