落尘小说

Chapter 2 The structure of cells（第2页）

&hertypeoffatcell，termedbrownfatwhichfatisbrokendowbyaprocesstermedthermogenesis。Inhumahemostbrownfatcells，usuallyintheshoulderareas。Itwasthoughtthatbrownfatwaslostbyadulthoodinmosthumans，butinsmallmammalssuchasratsandmice，whereheatlossisgreater（fromtheincreasedsurfaeratio），brownfatcellsareretaihroughoutlife。midratsshowsthattheyoffexcessfoodi。Althanimalsbuildupmassivestoresofwhitefattomaintainthemselvesformonthswithoutfood，theirbrownfatlygetswitatthetimeofwakingtoraisebodytemperature。WhenateiquecalledPET（positroomography）sgbecameastandardmedigteiqueafewyearsago，somepatients（wearinggownsonlyandthereforeysterypatetabolicactivityaroundtheshouldersandbackthatdisappearedinwarms。Thesepatcheswerebroeredintoactivitybythecold。Adultsdoiainbrownfat，andsomeindividualshavesignifitlymorethanothers。Alikelyreasonwhysomeindividualseatasmuchastheylikewithoutgaihattheyhavemorebrownfat。Intheory，ifwecouldswitchourwhitefattobrownfatcellswecouldeatasmuchasiththeendpoierratherthanfatter。Browhemselvesdifferfromwhitefatcellsbyhavingmaodria，withtheiroodriaprodugthebrowncolouration。ThenormalmitoetabolismwhierateseoredasATPisalteredtoproduceheatbyaprocesscalledprotonleakage，produgproteihermogeniioditions，suchasdeepseadivers，appeartoaccumulatemuchhigherthannormalamountsofbroosits，indigthatbrownfatberegeedinadults。Ifwhitefatcellscouldbevertedtobrownfatcells（ashasbeeissueculture），thenwecouldhaveausefultoolileagaierally‘burni。

Modifioflipidprodu

Inplantetiipulationofthemeationoflipiddropletshasstaggeringimplisforseedcrops。Thebiochemistryofproduofoilsinplantcellsfollowsverysimilarroutestolipidsinanimaldonegroupofehediacylglysferaseswhichcatalysetriglycerideprodu）havealreadybeeiipulatedtoapproximatelydoubletheyieldofoilandoleimaize。

&oskeleton

A‘skeleton’instantlybringstomindthebosofalongdeadindividual。Theloyofbohedepositionofmineralssuchascalciumphosphateirixbycellscalledosteoblasts，gthestructuralrigidity。Ihebohehumaoherwithtendonsas，flexiblyattachedtoeachotherasasystemoflevers，readytogewhichisdrivenbymustra。Therearestructureswithsimilarfunswithincells，wheremicrotubulesplaytheroleofleversandthe‘muscle’activityisprovidedbyaentsinassoyosin，whichslideovereachothertoprovideuchastheydoiself。However，uiverigidityandpermanenusculo-skeletalsystem，thecharacteristicofthecytoskeletoremeplastiddynamism，whereposbebuilt（polymerized）frombuildingblockseedandjustasquicklyremovedbybeingbrokendown（depolymerization）。Theold-fashionedideaofacellasessentiallyaballoohjellyoremisleading;cellshapeiswithin，modulatedbysignalsretheexternale，andcapableofrapidrespoinuallygetheirshape，gepositioheirneighbours，mhsolidtissues，ortakelongjourneysaroundthebodybyenterihebloodstream。Addtothisthereanizatiooskeletooseparateesatdivision（aswillbedesChapter4），andthedynamiatureofthecytoskeletosmaiic。

Aoskeletonisapropertyrestrictedtoeukaryotes，althoughsimilarproteiiaryformieria。Theeukaryoticcytoskeletonisdefinedasaworkofthreetypeseproteins:microtubules（formedfromthesmallerprotein，tubuliefilaments（agroupoffibrousproteinswithsimilarproperties）;andmiehesmallerprotein，a）（Figure　6a，b）。Eachoftheseproteinshasmanyassociatedproteihemfulflltheirrolesinjustabouteveryaspectofcellularfun。Althougheachoftheelemeoskeletonprovidesspecificpartsoftheoverallfuoproduceshapedmovemeothinkaboutthecytoskeletonisasaedsystem，involvingallpoher。Aswellaswholecellrespooskeletonalsoplaysaovihincells，wheremicrotubulesihmotorproteinssuein，providing‘railwaylines’formovementofvadcargahroughoutthecell。

6。Cytoskeletos。（a），（b）Theworkupthecytoskeletonofintactcells，exposedbyremovalofiellesleavingjusttheucleus。（c）Microtubules，thathavebeeesttube。（d）Sethroughaflagellum，showingthe9+2arraheaxoihasutentacle，showiubulararrayswhidthefoodal

&herornotfibrousproteiheoequivalentstructuretothecytoskeletoroversial。Becausethecytoskeletonissoobviouslycrucialtoiization，itissurprisingthattherehasbeensucharesistaoaureintheheproteinaeofthemaialpos，wasfirstisolatedfrommuscleover7o。Now，‘iedasaroutioplasm，andisiohecell。Moreretlystill，ahasalsobeeacceptedasatofthenuingpartofa‘al’arraofloousproteinsalongwithiefilamentsofthenuclearlaminawhichprovideafibroussgfementofents，fthe‘on’（seeFigure7Chapter3）。

dflagella

Whip-like‘tails’havebeenobservedonsingletheearliestdaysoflightmicrosthelate17thtury。Usuallyowosuchtails（flagella）movethecellthroughanaqueousmediumbypropagationofaseriesofwavesfrombasetotip。Ihelialtissuesliningsanssuchasthelungs，cellsarenumerousflagella（calledlargenumbers）whichmoveasurfauthewindpipe，ciliabeattogetherinatoandfromatlymovinglayerofmucusupwardstowardsthelarynx，thuspreventinganyacofpoteiveageorytract。

&eriaalsopossessflagella，buttheyarerelativelysimple，gidhelicaltail，whichactslikeapropeller，rotatedatitsbasebyamolecularmotor。Eukaryotidflagellaarerootedwithinthecellbyastructurecalledabasalbody，aheirwhip-likemovementwithiheflagellumitselfbyasystemofmicrotubules，aoastruownasaeDo，inhisclassic1961work　TheCell，‘fewcellularactivitieshaveprovedmorefasgtocytologiststhandflagellarmotion’。In1887，Jensensquashedspermflagellabetweenamicroscopeslideandclass，desghowthespermtailswere‘frayedintoanumberoffibrils’，some60yearsbeforethiswasedbyeleicroseManton，anEnglishbotanistwhohadmaaronmicrosthepost-war‘LeemfromtheUSA，showedthattherewere11fibresinallplagthoseinanimals，ingthatflagellarstructurehasbeeacularlyservedthroughoutevolutioandard’axouresistsofatralpairofmicrotubulessurroundedbyniubules（Figure　6d）。Withihebasalbodyisformedbyashortderofmicrotubuleswithoutatralpair。

Whatmakesamicrotubule?

Eachmicrotubuleisaholloallmadeoutofaproteiubulin。Twomoleculesoftubulinformadimer，whichresemblesashelledpeanut。Thesedimersjoioendmakingaloofilament），and13protofilamentsarejoihwisetoformthewallofthehollowtubethatmakesthemicrotubule（Figure　6c）。Thewholestructureisstabilizedbyassociatedproteins。Intheaxonemeofflagellaandentisproducedbyamotorproteineinwhiksadjatmicrotubulesandallowsthemtoslideovereachotherinasynaoprodudthattravelsdowntheflagellum，gthe‘whiplash’movement。thatthelihedyneinarmsaubules，whichweredisthe1950sbyBjornAfzelius，aresuccessivelymadeaherlikegaropehandoverhand。

Shouldflagellardyedorabsehecesaresignifity-fiveyearsafterhisinitialdiscoveryofthedyneinlinks，AfzeliuslookedatthespermoffourpatientsataySweden，andfoundthatthedyneiiailaxothespermwere‘nonswimmers’，whily，ledtotheiy。Halfofthepatientsalsosufferedfromaknownas　situsinversus，wherethemajansoftheviscera（heart，spleen，andpancreas），whiallyosideofthebody，beeswitchedtht。Thisturoresultfromalagciliaearlyinembryodevelopmeheleft–rightbodyaxisisestablished。ThisiscalledKartagener’ssyerMaageheinthe1930s。

Aparticulartypeofciliumisfoundihese‘primarycilia’asorystructures—ratherlikearadioaerialforginformatioesurroundimoveily，astheylackboththetralpairofmicrotubulesanddyneiheperipheralubules。Primaryciliaarenowknowntohaveawholehostoffuns，agasreeidchemicalstimuli。Intheliningofthenose，modifiedprimaryecttherethespecializedcellsoftheolfactoryepitheliumiiobs）wheresmellispertheeye，thespecializedphotoreceptorsoftheretiachedtotheircellbodiesbyaprimarycilium。Theprimaryciliumalsoplaysagroleincelldivision，andisalmostlyinvolvedinotion。

Diseasescausedbydefectiveciliaareknoathies，andtheyincludeawideraoms，egorizedasseparatesyndromesloheunderlyingoncellularcausewasidentified。Somesymptomsmaybeontoallpatiehersareuswithoral-facial-digitalsyndromesufferfrompolydactyly（extrafioes）andkidientswithBardet–Biedlsyidehelate19thtury）alsohavekidinadditionsufferfromretiionwhileadtoblindness，alongwithobesityaes—allasaresultofiivecilia。

Intracellularmicrotubules

Microtubuleswerethoughttobelimitedtoaxoilimprovemeronmicroscopypreparationtheearly1960sresultedintheirdischoutthe。Becausetheyalearedasstraightrods，theywereinitiallythoughtidastructures。However，LewisTilershowedthatbymerelygaprotozoaioarourigrade，allthemicrotubule-supportedsionscollapsedasthemicrotubulesbrokeapart，subsequentlyre-fafterafewmiroomtemperature。Notuntilthe1980sdiditbeeapparentjusthowdynamicmicrotubulesactuallywere，whenTimMitshowedthatmicrotubulescouldessentiallycollapseandre-forminseds，aprocessthathetermed‘dynamistability’。

Microtubulesalsoformtheframeworkofthemitotidle，bywhichtheesaredistributedtodaughtercellsatdivisioer4）。Byexposingdividicallede（whidstotubulinandstopsitjoioformfilameioidlehibited，‘freezing’theprocessofdivision，andagosomeanalysis。ewastheagrediesfromtheautumnautumusedbytheaiansforarthritiditions。Inhibitionofmitotidleformationalsobeachievedbydrugsthatstabilizeicrotubules，preventingthemfrdowore-formasspiubules。OnesuchdrugisTaxol（extrathebarkofthePacificyew）。Taxolbecameapotentialbliment，andbecauseremovalofthebarkkillsthetree，demandforthebarkalmostcausedthelossofallPacificyewtreesintheUSA。Fortuaxolwassubsequentlychemithesizedaspaclitaxel。Duetotheacceleratedrateofdivisionofcercells，almsthatihmicrotubulesaioialcertreatments。

Culturedfibroblastshavebeenthecellsofchoiceforthestudyofmicrotubulefun。Fibroblastsarefoundiissuesuts，ligaments，andtendrowninculturearelongandfiattened，ahesurfaceoftheculturedishwithabroadleadingedgeandanarredge（Figure　3trast，epitheliastayfiattenedandmaure（Figure　3b）。Inallculturedcells，icrotubulesradiateoutwardsioplasmfromastructureclosetothenucleuscalledthee。esactasamicrtre，gtheturnoveranddistributionofmicrotubules。Theystructures（trioles）identicaltothebasalbodiesfoundatthebaseofeachflagellumorcilium。Thesetriolesopairs，positilestoeachother。Earlyincelldivisioeaooppositeeaubulesthatmakeupthemitotidle。

Itisashortteicalstepfrplasticflaskstasuitablee（achamberat37degreestigrade），allowiobeplaicroscopestagefcellstobeobservedastheygoabouttheirbusiness。Becauselivingcellsarelargelytraishardtoseemuchdetailticalsystemssuchasphaseicroscopy，whialldiffereherefractilepropertiesinthepoolightanddarkregions。Forthiscruce，FritsZerheNobelPrizein1953。Nowadays，virtuallyanyproteiagged’tofluoresillumihUVlight）bybinihthoseofaproteincalledgreeprotein（GFP，propernameaequiedfroma‘glowinthedark’jellyfish。Bygitssequeninoacids，GFPhassisfluorescepropertiesalteredandisavailableinblue，e，yellow，andredfluorestvarieties，allowingseveraldiffereobefollowedovertimeinthesameliviothistheabilityoflow-lightcamerastnalsfromjustafewmoleculespercell，togetherwithlaserilluminationandputerizedimagingandanalysis，andlivingcellstlyprovidesawealthofinformationthatwasunimaginableonlyafewyearsago。Nowadaysitisfeasibletoarticularlivingcellproeimicros‘flashfreeze’theterestinmillisedprepareitforexaminatioronmicrosyprobescalledquantumdots，whicharebothfluoresicrosdeleseforeleicroscopy，allowlabellingofthesamemoleculesforbothteiques。

Aninitialbrieflookatmostlivingderthephaseiightbedisappointiiated，asdealappearstobegoingon。Uniswillzoomarouime，drivenbytheirflagellaordamoebaecraeedeasytoseeiime。Forculture，thecellularactivityseeninpopularseswillinvariablybetime-lapsefootage，withindividualimagesrecordedatintervalsofafewsedthenplayedspeededup。Inthisway，thehouracelltakestodivideisrecordedwithoenseds。Playingtheimagesbackat25framespersepressestheprotojustuenseakingitappearmuic。

&efilaments

Therequirementsofamotilelifestyleinanimalshaveresultediionofmeigthbypletelydifferentways。Whaoherasashell，asiosands，oraninteronasinfish，amphibiailes，birds，andmammals。Iheskeletalmaterialismadeofproteiedbydinsomeeralizedfidity。Thismaterialisknowracellularmatrix。Withinindividualanimalcells，meigthisprovidedbyagroupofproteiermediatefilaments，high-teflexiblecableswhichpermeatetheentirecell。tissuesarejoiheirneighboursbystrengthenedmembraionscalleddesmosomes，whichoredbyiefilaments，providiwhoutthetissue。

&efilamentsaresoatoftheirdiameter（10res）whitermediatebetweenmients（6res）andmicrotubules（25houghafilamentsandmicrotubulesarethesameineverygplants），aefilaments（lamins）intheandard，itermediatefilamentsarespecializedagtotheirtissuetypeandembryin。ectivetissuesarecharacterizedbyaefilamein，whereasneurofilamentsarefouissue，anddesminischaracteristicofvertebratemuscle。Keratinsarealargegroupofiefilamentsfouhelialiuralproteinofskiisidethehair，wool，fingernails，horns，ahese‘hard’keratiableextracellularsesalydead，althoughtherearemaoplasmisthataredynamic。Mutatioinsskin，gaknoidermolysisbulleionblisteriitbelifethreateningtone>

&filamentousproteinsinthecellarecalledmients。Theyarearound6resihatofiefilaments，aheproteina。Aisagl-a），butittakesadifferentform（F-aassembledis。Filamentousaistheobuworksbyahostofadingproteins，fatleast15differentstruheastoesbackover60years，tothe1940swhe-Gyiestablishedthepresehadmyosininstriatedmuscle。Furtherworkinthe1950sbyAndrewHuxleyandHughHuxley（uablishedthatwhes，afilamehemyosis，aionwhisthemuscle，produgforce。TheofATPtoADPreleasestheneergyforthismoleteratotakeplace。Musclehasahighlyeometricalmoleculararchitecture，whereeverymyosinmoleculeissurroundedbya‘der’ofsixamoleculesallowingthemoleculestoslideovereachother。Thisarraisonlyfoundinmuscleahepossibilitythatadmyosinteracttoprodutraon-musclecellsseemedunlikely。However，in1973，TomPollardshowedthattherewasmorethaypeofmyosininnon-musclecells。thatthereareover40differentmyosinsinmammals，andthat（alongwithF-a）theysupplythemotileforvolvedincelldivision，ent，aakeofexternalmaterialbydocytosis）。Aalsohasastructuralroleioskeletois，bouheproteinvillin，supportthefiionsofthecellmembrane（filopodiaandmicrovilli）。

Cytoskeletal–eras

Fromtheihehesurfaceofthecell，thereareliaboutallofthefilamentousproteins。Thelaminswithinthenucleusareaediatefilameer3），whicharejoioplasmitermediatefilamentsbypresthatcrossthenuvelope。Allthecytoskeletalelemeoeachother，withdirelinks（plakiermediatefilamentsandmicrotubules，aermediatefilamentsandthemientsthatformthethirdmajorelemeoskeleton。Thisieinsicrotubules，iefilaments，andmients，allwithdiffereies，funstogethertomaiuralandmeitegrityoftheasabilitytomove（seeChapter4）。

Withinalivihreecytoskeletalposworkinunison，asmightbeexpectedafterfourbillionyearsofevolutiohepohecytoskeletonindividuallyislikedesgapistoingrod，andkshaftwithoutmentioningawihcasesthewholeissiderablymorethahe>

Thirtyyearsago，whenDonaldIngberwasaeatYaleUy，hewascedthattheviewofthecellasa‘rubberbagfilledwithjelly’wassomewhatoversimplified。IriguedbytherevolutionaryarchiteinsterFullerinthe1940s，whocreatedaseriesofrobuststructureses（inghisownhouse）。Geodomesarestruashellofmultiplesmallrigidtriaanymajstructuressuchasbeamsorns。FullerhimselfhadbeehesculpturesofKehSnelsidstaieelrodsappearedtofloatinthinair，butareactuallysupportedbyasystemofcables，ratherliketheriggingonasailboat，wherethemastiskeptinplacebyabalaensionahemastitselfisrigidioresistthepressiohetensionintheriggiureisrobust，andwillonlyfailifthemastbucklesbreaks。Thisistheprieyrity，whichoffersthemaximumamouhforthemiureyandmaterials。Ihattesineverycell，mediatedbyrigidmicrotubuleswhichresistthepressioiefilamehusgehwithinallcellshapes，betheyfiattenedhexagonaldihelia，orextendednerveaxoncellswhichmaybeametreieyisatworkevenwhenagesitsshape，ashappensindivision。Ieedcellswillroundupatthestartofdivision，thenpiwhtercells，whifiatteheedgesfiatten，trianglesformedbyafibresareclearlyvisiblearouhsixneighblesfahexagolyliketheedgeofaBusterFullergeodome。Thefiattensfurther，gshapetoatypidedfibroblastfattatsbetweenthemembrahebaselayertermedfocaladhesiratingasasingletrast，cellsgrowninculturefromepithelialtissueswillattachthboursandmovearoundasasheet。Asinliviheepithelialcellsattachtoeachotherwithstructurescalleddesmosomes，whicharetoughplaque-likestruedbyloentofthecellmembrane，ahiermediatefilaments。Inskin，atissuetlybeched，epidermalcellshavemultipledesmosomes，aermediatefilamehenedbynumerouskeratis（Figure　6a，b）。Whehrougheverycell，thisarraesaoughtissue。