Membranes(Lecture7):Membranesareveryfluidinordertoallowproteinsinsertedintothemembrane(integralmembraneproteinsortransmembraneproteins)tointeractwitheachother.Usuallymembraneproteinsareintegratedintothemembranebymeansofoneormultiplealpha-helices.Thisworksifallaminoacidsmakingupthealpha-helixarehydrophobic,becausetheirsidechainsarepointingoutwardinteractingwiththelipids,whereasthehydrogenbondsneededtostabilizethealpha-helixareallalongthelengthofthealpha-helixcylinder.Theinsertionofmembraneproteinsintothelipidbilayerintroducesanasymmetry,becauseintegralmembraneproteinscanonlymovelaterally,notvertically.Thismeansthesideoftheproteinpointingoutwardneverchanges,theproteinjustmovesaroundwithintheplaneofthemembrane(likephospholipids).Freezefracturesplitsmembranesintotwolipidleaflets;why?Becausefreezingtightlybindsphospholipidstosurroundingwatermoleculesbyhydrogenbonds,whereasthetwolipidleafletsareheldtogetheronlybyvanderWaalsforces(inthefrozenstate).Themainfunctionofmembranesistoserveasabarrierandtoselectivelytransportmoleculesthecellneedsorwantstogetridof.Toanalyzemembranes,scientistsprepareabeakerofwaterseparatedintotwocompartments.Thedividercontainsasmallholecoveredwithanartificialmembrane.Thensolutescanbeaddedononeside,andafteracertaintimeonecanmeasurethesoluteconcentrationontheotherside.Thisexperimenttellsyouthatmembranesareselectivelypermeable.Gaseslikeoxygen,andsmallpolarmoleculeslikewaterpassfreelyacrossthemembrane.Largechargedmoleculescanbarelycrossthemembrane,andionsnotatall.Wheneverthereisadifferentconcentrationofsubstancesacrossthemembrane,thisgivesrisetothephenomenonofdiffusion:thepassivemixingofsubstancesresultinginnettransportalongtheconcentrationgradient.Tofillthisdrydefinitionwithsomelife,imagineabouqetofrosesinthemiddleofaroom;youallknowthatasyoustepcloser,theywillsmellmorestrongly:thereisaconcentrationgradientofscentmoleculesmixingwithairmolecules.Ifyouthrowouttheroses,whathappenswiththeconcentrationgradient?Itwillgetflatterandflatter.Youcanseethatifyoudrawawindowacertainpositionawayfromtheoriginx=0,wherethemoleculesallstartoutfrom,moreandmoremoleculesmoveintothatwindowovertime(netmovementawayfromthesource).Themovementofindividualmoleculesis,ofcourse,random,andisowingtoBrownianmotion,therandomwalkofindividualmoleculesbecauseofthermalmotionsandcollisions.

YouhaveBrownianmotioninawaterglass,butnodiffusion;addadropofink,stillBrownianmotion,butnowalsodiffusion,becausetheinkwillequallydistribute/diffusethroughouttheglassofwater.Inotherwords,diffusionoccursaslongasthereisaconcentrationgradient(-G).Whenasmallmoleculelikeglycerolisequallydistributedonbothsidesofthemembrane,itstillmovesbackandforthacrossthemembrane,butthereisnomorenetmovement,hencenomorediffusion(G=0).Hightemperature,smallmoleculesize,shortdistancealsospeedupdiffusion.Aswaterissuchanimportantmoleculeinbiology,thediffusionofwateracrossaselectivelypermeablemembraneiscalledosmosis.Ifyouplace1.05Lofwaternextto200gofNaCldissolvedin1Lofwater(1.05Lofsolution),therearemuchfewerwatermoleculesinthesolution(0.05Llesswater),thereforewaterwillmoveintothesolution(alongitsconcentrationgradient).Hypertonicsolution:oceanwatercannotquenchyourthirst,becausewaterwillflowoutofyourcellstodilutetheoceanwater.Hypotonicsolution:tapwater,netwaterflowintocells.Tapwateristheleasttoxicsubstance,butyoucanstillkillyourselfbydrinkingwater:Untrainedmarathonrunnerdrinkingseverallitersofwater.Isotonic:samesoluteconcentrationasinsidethecell,thereforenonetwaterflow.Totransportmoleculeslikeionsorlargepolarmoleculesacrossthemembrane,cellsneedintegralmembraneproteins.Theycomeintwoflavors:thosethatjustfacilitatediffusion(passivetransport),andthosethattransportmoleculesagainsttheirconcentrationgradient(activetransport).Passivetransport:facilitateddiffusion1. gatedchannelproteins:ionsflowalongtheirelectrochemicalgradientwhenthechannelisopen2.carrierproteinGlucosecarrier:bindingofsugartoeithersidecausesaconformationchangeinthecarrierproteinresultingintransportofsugartotheotherside.Sugarcanbetransportedinbothdirections!Incontrasttochannelproteins,carrierproteinscanbesaturatedbecausetheymustbindtheirsubstrate,i.e.atonepointtherateofdiffusioncannotincreasefurtherbecauseallcarrierproteinsareoccupied.Saturationdoesnothappenwithchannelproteins.Channelproteinsarealwaysgated,thatis,theyareclosedintheirdefaultstate,andopenuponchangesinelectricityorbindingofregulators.Channelproteinstransportionsalongtheirconcentrationgradient.

Importantly,bothchannelsandcarrierscantransportsubstancesonlyalongtheconcentrationgradient(thatswhyitscalledfacilitateddiffusion)!Activetransportmovessubstancesagainsttheirconcentrationgradient,andthereforerequiresenergy.Thisissubdividedintoprimaryactivetransport,whichdirectlyreliesonATPhydrolysistoovercomethe+Goftransportingsomethingagainstitsconcentrationgradient,andsecondaryactivetransport,whichusestheenergyfromtheconcentrationgradientsetupbyprimaryactivetransport.Mostimportantexample:Sodiumpotassiumpumpinanimalstocounteracthypotonicdrinkingwater,notfoundinplants,becausetheyhaveastablecellwallthatpreventsburstingofcellsuponwaterinflow.Thesodiumpotassiumpumpmovesthreesodiumionsoutandtwopotassiumionsin(anetmovementofoneionout).Thiscontrolsosmolarity,generatestherestingpotential,andsetsupiongradients.Secondaryactivetransportsystemsusegradientsestablishedbythesodiumpotassiumpump.Animportantexampleisthesugarsodiumcotransporter,whichusestheenergyfromsodiuminflowtotransportsugarintocellswithahighinteriorconcentrationofsugar.Thebestexampleisthecellsliningthegut,whosetaskistotakeupnutrientsfromthefoodweeat.Tomaximizetheuptakeofsugar,thesecellsuseasodiumsugarcotransportertotakeupeverysugarmoleculefromthegutlumen(wherethedigestingfoodpassesby).Ontheothersidethesugarcrossesthemembraneintotheextracellularfluidwithasugarcarrier,becausethesesugarmoleculesareconstantlyremoved/shippedtotherestofourbody.