Chapter 2 The structure of cells（第1页）

Chapter2Thestructureofcells

&iccellssharethesamebasiclayout，inthattheyaresurroundedbyamembrane，ahwithinwhichthereisavarietyofmembrane-baperformspecializedtasks。ahenucleuswhisDNA。Atroughlyohousandththevolumeoftheeukaryotee，theanizationofaprokaryoteisrelativelystraightforwardbyparison，althoughbacteriapossessverysimilarstructuralaspedmaerytoeukaryoticcells。Theircellmembrahesamelipidbilayer（illdisext）andtheirmolecularmaerysuesforproteinassemblyfunuchthesamewayaseukaryotes。Bacteriadohavespecializedcellstruotilitysuchasflagella，andmaypossessinternalmembrahecaseofagasvacuolethatservesasabuoyancyaid。However，theDNAinabacterialcellisasinglecircularmoledthereisenuent。

Thecellmembrane

Allcellsareenclosedbyaboundarystructure，theplasmamembrane，whichprovidesabarriertootherdtheexternalehoughthemembraaients，unis（bacluded）usuallyhaveextramaterialosideandplantcellsarecharacterizedbyarigidcellwallofcellulose（Figure4）。Overaturyofiionhasshowobeanincrediblypliddynamicmixtureoflipid（fat）moledproteins。Althoughthebasicstructureoftheplasmamembraremelythin-justaoleculesthiingalipidbilayer-itisextremelytoughandflexible，aoallowforthetexoleculesbetweessurroundings。Thisisachievedviathewaterthattlyentersasinaannerbringingsolublemoleculeslikeoxygen（neededasafuel），aissuchasdieexternalmaterialbephysigulfedbythemembrane，aproasphagocytosis。Thereverseprocessisexocytosis，inwhichamembrane-bouerialdestireachesthecellsurface，atwhiembranesfuseahethetswiththerityofthemembrahedynamiatureofthecellmembraneissuchthattheentireplasmamembraurnedover’（replahourlybasis。

&heearliestexperimentsinvolviionsoflipidsaoexplaiiesofmembraneswereperformedtowardstheehtury，oableinGermanybyAgnesPoesstudiedthebehaviourofoilpouredontowaterinaflatdish，identifyingtheinfluenpuritiesonthesurfaoffluids。Sheseh，whowassuffitlyimpressedtogetthempublishediifialNaturein1891。In1932，IrvingLangmuir，winNewYork，rizefthatlipidsspreadonroducealayeronlyohidthatallthemoleculeswereoriehesameway。Thishappensbeeendofthelipidmoleculeisattractedtowater（itishydrophilidtheothereishydrophobic）。Eachlipidmoleculeisshapedlikeanold-fashiohespeg，withthetopofthepegbeingthehydrophilidthetwolegsofthepegrepresentingthehydrion。Allthepegsfloatonthesurfaceofwaterheaddown，legsuppermamonolayer。IerandJamesGreedmembranesfromredblooddingthatmembraneoftwolayers（abilayer）oflipids，makingasandwichwiththehydrophilicpegheadsosides，andthehydrophobitheihereiswaterbothisidethecell，thisarraismaintaihhydrophetherontheihemembrahisarrawasdirectlyvisualizeddecadeslaterwiththeadveronmicroscopy，wherethihighmagnifibrawodarkliedbyalightregiohem（see，forexample，　Figures　4and141935，JamesDanielliandHughDavsohislipidbilayerwasbothsidesbyalayerofproteilasteduntil1972whenSeymarthNisuggestedthattheproteinscouldalsobethreadedthroughthelipidlayers，afromeithersideofthemembrahthisfiguratioraeins，andasiweaveitswaythroughthelipidbilayerseveraltimes。Thelipidmoleamembranearehighlymobile，tlymovingpastohemembraeiothedesofthe‘fluidmosaie。ThisactivityofthelipidswasedbyMichaelEdidinin1970，whehemembranelipidsoftwodiffereypeswitheithergreenorredfluorestchemicals。Thisgavea‘patchwreenlabellingfromindividualcellsgrowherinamixedcellculture。Edidinthenaddedvirusestotheculturewhichcausedthemembranesofadjatcellstofusetoeachother，thusmixingtheirmembranelipidsand，withinanhreenpatchesoffluorescewerereplaelabelling，showiemixingoftheindividuallylabelledlipidmoleculeswithinthefusedmembranes。

&hroughaplantcell，showingthemaindifferenalcells:acellwalloutsidethecellmembrane，chloroplastswithstars（SG）ihem，andalargevathetreofthecell

Withinthisotionofthelipids，groupsofmembraarouhelipidbilayerratherlikeicefloesinthepolarseas。Sometimesafewlipidmoleculeswillformaclusterforafewsedsgspecializedareascalledmembras。Membrasweredislyredtheirfunotyetpletelyuood，althoughitseemslikelytheyareinvolvedinsigweeherearearound500differentmembranelipidswhidandanchordiffereelsthroughthemembraroltheuousflowofmoleculesacrossit。

Theseelsenableaomaintainaninterionofsodiumthatisoheexterion。Thisrequirestpumpingtoremovesodiumwhichotherwisewouldraisetheosmoticpressureinthecellwhiturn，ater，withthepotentialtoburstthecell。Atthesametime，potassiumismaihiamuchhighertratioerhesamemembranepumpbringspotassiumieassodiumispumpedout，anactivitythattakesaboutohirdofthetyofthecell。

Proteihesurfabraasreceptnallingmoleoutsidethecell。Thesemessagesarethenpasseddoweinswithiheoswites，ifrequired，ieredonessusulinwillidirectlywiththemembrane，alloassiuallyeverythingthatgoesoherinfluences，orisinflflflueheabras500typesoflipidmoledupto10，000typesofmembraeins。Cells‘feel’theirimmediatesurroundingswithfififiensionscalledmicrovilli（seeFigure3a–eepithelialcellssuchasthoseresporieheguts，themembranebeesfashiooabrushborder，wheretightlypackedmicrovilliihesurfacearea30-fold（seeFigure14inChapter5）。Whileitisimpossibletoprioritizevariouspartsofthecell，astheyaremutuallyi，withoutmembralifeotexist。

Membranesinsidecells

Membranesarealsocruciallyimportantiworeasons:first，toprovidesurfawhichchemicalreaprodsedlytoprovideseparateareasiheicalreastoproceedwhichmightotherwiseiheachother。Iheinnersurfaceoftheplasmamembrahepositiwithinthedprovidesattatpointsforintracellulartsthatobeinspecifis。Usingtheanalogyofthecellasafactory，theinternalmembranesprovidetheworkbenches，floors，gs，andwallsforallthedifferentpartsofcellprodu，withtherallypositioheoffiwhiformationisstored。Insmallcells，suchasbacteria，whichareusuallyrodshaped，theiheplasmamembraneprovidesalargesurfarelatioerior，sothatanythingthatneedsafixedpositionbe‘hung’ontheinside，alybadotherprenerallyhavelittleornointernalmembraioheinternalvolumeofeukaryotecellsisathousaofabacterium，sothattheeukaryoticcellrequiresavastinternalmembraemaroundahuheareaoftheplasmamembrahisiionofbiochemicalactivitiesiscrucialastherearehundredsofchemicalreasgoingonthatseriouslyiheachother。Prokaryotes，withnointernalmembraestosomeextehisproblembyaggregatinggroupsofspezymesintomultiproteinplexes，whichworkasfreeentitiesiheadditioesediffereabolicprocesseswithinmembraments。Themajorinternalmembraemiiccellsistheendoplasmicreticulum（usuallyshorteoER），whisahroughouttheehispartofthecelliscalledthe（everythihecellmembraneexgthenucleus;Figure5a，b）ahinginitissurrouheplexmixtureofsubstancesdissolvedinwater，likeaveryolecularsoup’。

5。Internalcellmembraructures。（a）Thenuvelope

&esthehe，whisanellesingmito）andendoplasmicreticulum（ER）。（b）Amitosurroundedbyspiralpolyribosomes（r）attachedtothesurfaceoftheER。（uplex，elarrowed。（d）Golgibodies（Go）prisedofstabranes

anelles

Twaheitodriaand，inplants，chloroplasts—havedouble，ratherthansinglemembrahisismostlikelyahangoverfromwhentheywerefree-livingformsearlyincellularevolutioheywereiercell，theirownmembranebecamesurrouhecellmembra。BothmitodriaandchloroplastsA，furtherevideheywere。Therearetwotheoriesastohowchloroplastsandmitodriabecamepartofeukaryoticcells:theycouldhave‘iheeukaryotecellor，alternatively，beenengulfedbyalargeriionshipinwhichbothpart。

&iccellprovideda‘safe’e，inwhichthemitehatcouldbeharvestedbythehostd，inplantcells，chlorlucosebyphotosynthesis。Inmityisprlucosebyaprocesscalledoxidativephosphorylation，whichothesurfaternalmembraae（Figure5b）。Inchloroplasts，glucoseisproducedbyphotosyizymesinstabrahylakoids（Figure4）。

Allothermembrane-banelles（colleownasvacuolesorvesicles）haveasinglebilayermembraypicalcellwillhavearound1000ofthesevadasimilarodria。Secretoryvesitainchemigerssuonesforreleasefromthees，lysosomes，andperoxisomes（seeFigure2）allvariousmixturesofeeinsthatcatalysechemicalreas。Lysosomesbelikeomachofthecell，astheyhydrolytizymesthatbreakdownbiologicalmaterialintoitstpartstoprovidefoodfortheesalsofusewithphagocyticvacuoles（phagotainierialsuchasbacteria，killingaheinvadinganisms。TheBelgiadeDuvediscoveredlysosomes，forwhichhereceivedtheNobelPrizein1974。Healsodiscoveredperoxisomes，whichreplicatebydivisioodriaandchloroplasts，butdoheiroeroxisomesareinvolvediyofbiochemicalpathwaysandatleast50differeheyareimportantinthebreakdown（oxidation）ofsubstancessuchasfats，providingamajorsouretabyina，andplantcells。Beeoftheproductsofoxidatienperoxide，whichisharmfultotheesalsoenzymecalledcatalase，whichbreaksdownthehydrogeer。

Peroxisomesarealsositesofsynthesisofseveralehoseinlivergrespoheproduofbile。Aswithmostindividualaionsinperoxisomeformationhaveseveredaingwillusuallyleadtoafertilizedeggfailiafewdivisions。

&eofproteinproduforthetsofthevariousvacuolessuesandperoxisomesisatthemembraheERwasdiscoveredbythreepioronmicroscopy—KeithPeePaladeinNewYorkandFritiofSjostraheearly1950s。Eleicroscopyallowsa1000-foldiailparedtoallightmicroscopy，butimposesdiffithepreparationofspethataronbeamlypassthroughextremelythiiohediffieioronmicroscopy，Porterandhiscolleaguesopeureinareviouslyunimagiroke，indistindirregularshadowylumpsfromlightmicroscopywerevielydistinellessuchasmiture　5b）。InthewordsofDo，acolleagueofPorterandPalade，‘fists，thede1950to1960heldthesameantiaattendstheopeniiioatlasesofbiologicalultrastruaillclassicstothisday。

&hecell

MitodriawerefirstisolatedbiochemidanalysedbyAlfredLehningerin1949，ingthepreseheenzymesrequiredfeionbyoxidativephosphorylation，ahighlyeffitprowhitsareoxidizedtoproduosiriphosphate（ATP）。Theenergyfwork，buildingproteinsandmovingthingsarouoredinamoleculeofATP。TheePisstoredin‘highenergy’phosphatebonds。Tovolvedbiochemicalprocessshort，thisehereleaseofelethecitricacidcythemitoembraingATPsynthase，aheP。EnergyisreleasedfromATPwheebondsarehydrolysed（aprocesswherethemoleculeissplitintotwopartsbytheadditionofamoleculeofwater）。Withthereleasey，ATPisvertedtoADP（adenosinediphosphate）whituredbacktoATP，staiherelease。

OnlythreeyearsafterLehninger’sbiochemicalcharaitodria，Palade’seleicrographsshmembraure（Figure　5b）。Theorderofthesediscoveriesrefieoveralltrendthatthe‘grindandfind’wsofbiochemistryhaveofteedseminalinformationosiheiractualimagironmicroscope，althoughinthemicroscopist’sview，nothingparewithseeingwhatthetsofthecelllooklike。Thedifferentapproachesofthebiodbiologistbeillustratedasfollows。Presumeherhadeverseenawristwatch，butresehation。Afewdayslaterthebiochemistwouldreportthatthewatchhadbeenanalysedbyseparatingit（grindingitup）intoitspos。Thisanalysiswouldshowthatthewatchwasmadefromvariousproportionsofcopper，brass，steel，ahmaybeafewdiamonds。Thebiologistwouldhatagdohahebadreportthatitseemedtohwhichpoweredaseriescogwheels，thatdrovetwoarmsoofthewatchthatseemedtorotateatatspeed。Whilemassivelyoversimplified，thisparisongivesahediffereheanalyticalapproachofthebiodtheobservationalapproachofthebiologist。Fortunately，usedtogether，thesehavebeenfruitfulindeedincellbiology。

Proteinprodu

&otheER，themajorityofERmembranesarecoveredwithribosomes（Figure　5a）andareknhER，whilsttheremainderbearnoribosomes（smoothER）。Thejobofribosomesistomake（syeinsfromaminoacids，holdingandjoiningtheaminoaakepeptides，theidesaeins。AseriesofRNAmoleculesareieinsynthesis。IhehesequenucleotidebasesfthecodeforaparticularproteinisfirstplateDNAinaprocesscalledtrans，produewmoleessengerRNA（mRNA）。Messeheofthenudergoingmodifi（calledspligtheway。Ooplasm，ribosomesbindtomessengerRNA，whiactsasatemplatefortheliherofaminoatoproteins，aprocesscalledtranslation。

TheaminhttotheribosomebyshortRNAmoleownastransferRNA。ProteiheERehespa）betweentheERmembranes（Figure　5b），wheretheyarefoldedintoafinalfiguratipassedoessuchastheGolgibodies（Figure　5d）。TheGolgibiapparatus）isastackoffiattenedmembranevesicles，whereeinsarepatovacuolesfordistributihoutthedmayalsohavesugarsaddedinaproasgly。hesizedproteiriyd，shouldtheybedefeanyway，theyaretaggedbymoleculesofubiquitinforsroteinmisfoldirimeodisorderssuchascysticfibrosisaeinqualityeismsmaybeelesseffectiveaswegettoAlzheimer’sdiseaseande-relatedives。

&hesizedandfolded，eioreachtheirfiionwithinthegsttheotherbillionsofproteiahesizedanddegraded。Someproteihowomembranebarriersbefthesitewheretheyfulflltheirfun1971，GünterBlobelandDavidSabatinifromtheRockerfellerInstituteinNewYesteda‘signalhypothesis’，inwhisweregivenaluggagelabel，orzipcode，toeheyfiherightdestinatioakestheformofshortsequeninoaoogenials，whiattachtoreceptorproteinstoallowthemthroughmembraoreachthecorreation。In1999，GünterBlobelreceivedtheNobelPrizeforthiswork，laihemolecularmeismsbehindseveraldiseases。Bothcysticfibrosisandprimaryhyperoxaluria（agkidanearlyage）arecausedbyproteinsfailiheircorreatioedthemilliondollarprizemo-warrestruDresdehetryofhisbirth。

Lipidprodu

&sroleihesis，theERisaversatileanellewhibothredtransmitsignalsandactasacellularstoreforcaldisalsorespohesynthesisoflipids。Withinindividualcells，fatisproducedatthesurfaceoftheERastinyindividualdroplets（lipogehoughfatthatwearefamiliarwitharoundtheedgeofoursteaksandoftenaroundourwaistliobeinsolidhomogenouslumps，itallexistswithinmembrane-boundfatdropletsinindividualcellstermedadipocytes（seeFigure3d）。Givenauousirients，adipocyteswillaccumulatemoreandmorelipiddroplets，whichcoalescewiththeirneighbourstobeelargerandlarger，agforthevastmajorityofthee，whireaes‘normal’size。Obesityistlyadisybalaresultsfromtheuedacoflipiddropletswithies。AtthispoiregrettheefficyoftheER，besidesprovidingforfatste，theERalsosynthesizesehesmoothERtobreakdorocesstermedintracellularlipidhydrolysisorlipolysis。Thus，amajorfabodyweightisthebalahesynthesisandbreakdownoflipidsintheER。gthehealthcesofbeiissurprisingthatfatatthecellularlevelhasreceivedrelativelylittleattention，withlipiddropletsthoughtofashaedepots。However，udiesareshowianelles，andanythingbut‘lumpsoffat’。Alleukaryoticcellshavetheabilitytomakelipids，whichproduceallthenaturallyoilsandfats—fromrapeseedandoliveoiliomilkfats，lanolin，andlardinanimalcells。LipidmoleculesaretratedatthesurfaceoftheER，thenpiningadroplet（uniquelysurroundedbyasinglelipidmonolayermembrane）andremaiheER，wheretheecatalyselipidsynthesisarelocated。Mitodriaarecloselyassociatedwiththesitesoflipidprodu，providingtheenergyforfatformatioodriaareactuallytetheredtothesurfaceroupofmembraeins。Asmorelipidisaccumulated，individualdropletsfusewiththeirneighbwhichtheseparatemembraiallyprodugeverlargerdroplets（Figure3d）。Durihisprocessisreversed。Bigdrmeosmallerones，andenzymesfromsmoothERbreakdownthelipidmoleculesthatprhthemembrahesizeofthedropletfromtheoutsidein>

&ionoflipidsalsoocthedintheliningofbloodvessels，particularlyththewallsofmajorarteries。Hereacoflipidsleadstoformationoffattyplaques，resultinginatherosclerofthearteries），whichlimitsbloodflowandthusleadtoheartattadstrokes。Atothersites，iionofbloodflorodueyfailurerene。Excessiveacoflipidsisalsoamajorfatypetwodiabetesaeatosis（fattyliver）。Exptionofalgesitheliverbreaksdownas，leadingtomoreseveressuchascirrhosis。Fortuhefatdropletsstillbebrokendowniheisreversiblewithreduptionofalcohol。Allthisbadhereasoioherwemightteroffwithoutfatcells，buttheyfunrespoionarypressures，allowingfethatmayedussurviveintimese，andalsoallowingmanyothermammalstosurviveseverewintersbyhibernation。

Brownfatcells