MembraneStructure

lipidandproteincomponentsofbiologicalmembranes

JimHuettner

LectureOverview

•  History•  Lipidcomponentsandasymmetry•  Bioactivelipidmetabolites•  Membraneproteins•  Aminoacidsinthemembrane•  Lipidmodifications•  Subdomains(lipidrafts)

EarlyHistory•  Theabilityofoiltocalmthesurfaceofbodiesofwaterwas

recognizedinancienttimeshttps://www.youtube.com/watch?v=f2H418M3V6M

•  1700’s-BenFranklinperformedearlyexperimentswitholiveoilspreadingtoformamonolayeronapondsurface

•  1800’s-AgnesPockelsandLordRayleighcalculatedthethicknessofanoilmonolayerat13-16Angstroms

•  1900’s–LangmuirusedatroughsimilartoPockels’home-madeapparatustoanalyzesurfacetensionandconfirmtheearliermeasurements

WangDN,StieglitzH,MardenJ,TammLK.(2013)BenjaminFranklin,Philadelphia'sfavoriteson,wasamembranebiophysicist.BiophysJ.104:287-91.

BilayerHistory

•  1925-GorterandGrendelcalculatethatRBCmembraneshaveenoughlipidsfor2xthesurfacearea

•  1935-1960s–Davidson-Danielli-Robertsonmodelsenvisionedabilayerwithproteinscoatingtheinnerandoutersurface

•  1972–SingerandNicholson–FluidMosaicModel

Summaryofmembranemodels

RobertsonJL.(2018)Thelipidbilayermembraneanditsproteinconstituents.JGenPhysiol.150:1472-1483.

FluidMosaicModel

Lodishetal.,8thed.Fig.7.1

LipidComponents

o Phosphoglycerides•  PC–phosphatidylcholine•  PE–phosphatidylethanolamine•  PS–phosphatidylserine•  PI-phosphatidylinositol

o Sphingolipids•  sphingomyelin•  galactocerebroside(glycolipids)

o Sterols•  cholesterol

Amphipathicpolar,hydrophilicnon-polar,hydrophobic

chemicalstructures

Lodishetal.,8thed.Fig.7.8

phosphoglycerides

Albertsetal.,6thed.

ω-6andω-3cis-unsaturatedFAs

Sphingomyelin

Luckey,2nded.Figs.2.7&2.8

Glycolipids

Albertsetal.,6thed.

Cholesterol

Albertsetal.,6thed.

•  Mostprevalentinsurfacemembrane(uptoabout25%)•  Precursortobileacids,steroidhormonesandvitaminD•  Interactswithandstabilizessaturatedacylchains(sphingolipids)•  Broadenstemperaturerangeofphasetransitionfromgelstatetofluidstates

LipidCompositionVaries

Albertsetal.,6thed.

LipidMobility

Albertsetal.,6thed.

DistributionfromMDsimulation

Luckey,2nded.Figs.8.7&8.8

ThicknessandCurvature

Lodishetal.,8thed.Fig.7.11

BilayerPolarity

Lodishetal.,8thed.Fig.7.5

LeafletAsymmetry

Luckey,2nded.Fig.2.14

AnionicPSandPIaremoreprevalentinthecytoplasmicleaflet

LeafletCompositionVariesSource/Location PC PE+PS SM cholesterol

Plasmamembrane(humanRBCs) 21 29 21 26

Myelin(humannerve) 16 37 13 34

Plasmamembrane(mungbean) 47 43 0 0

Innermitochondrialmembrane(plant) 42 38 0 0

Outermitochondrialmembrane(plant) 47 27 0 0

ERmembrane(rat) 60 25 3 7

Golgimembrane(rat) 51 26 8 13

Innermitochondrialmembrane(rat) 40 37 2 7

Outermitochondrialmembrane(rat) 54 31 2 11

Primaryleafletlocation Exo Cyto Exo Both

Lodishetal.,8thed.Table7.1Composition(mol%)

EnzymaticModification

Phospholipasesites

Lodishetal.,8thed.Fig.7.12

Enzymaticreleaseofbioactivemetabolites:•  IP3anddiacylglycerolbyPLC•  LysophospholipidsbyPLA1orPLA2•  Arachidonicordocosahexaenoic

acidbyPLA2

MembraneProteins

Albertsetal.,6thed.

AcylModification

Albertsetal.,6thed.

C14 C16 C15farnesylorC20geranylgeranyl

GPIanchor

Luckey,2nded.Fig.4.10

AdditionalFeatures

Albertsetal.,6thed.

•  Oxidizingextracellularenvironmentpromotesinter-andintra-chaindisulfidebonds

•  Reducingintracellularenvironmentkeepscysteinesidechainsavailableforthioesterification

•  Extracellularoligosaccharidemodification•  Tendencyforanexcessofpositivelycharged

ArgandLyssidechainsinthecytoplasmicsegments

TMHelixAminoAcidPrevalence

Luckey,2nded.Fig.6.25

ΔGformembraneinsertion

Luckey,2nded.Fig.7.23

InsertionSignalVariety

Luckey,2nded.Fig.7.25

Lipidsubdomains(rafts)

Albertsetal.,6thed.

LipidRaftsAlbertsetal.,6thed.

Luckey,2nded.Fig.1.9

“Ballpark”Numbers•  “Typical”membraneincludesmorethan100distinctlipids•  Morethan500differentfattyacidshavebeenidentified•  Lateralmobilityinliposomessimilartooliveoilandabout100

foldslowerthanformoleculesinwater•  Inanimalcellsabout50-90%ofcholesterolisinthesurface

membrane•  Lipid/Proteinratiovaries:80%L/20%Pinmyelin,

25%L/75%Pinmitochondrialinnermembrane

AdditionalReading•  vanMeerG,VoelkerDR,FeigensonGW.(2008)Membranelipids:wheretheyareandhowtheybehave.NatRevMolCellBiol.9:112-24.

•  vanMeerG,deKroonAI.(2011)Lipidmapofthemammaliancell.JCellSci.124:5-8.

•  SezginE,LeventalI,MayorS,EggelingC.(2017)Themysteryofmembraneorganization:composition,regulationandrolesoflipidrafts.NatRevMolCellBiol.18:361-374.

•  JacobsonK,LiuP,LagerholmBC.(2019)TheLateralOrganizationandMobilityofPlasmaMembraneComponents.Cell.177:806-819.

DiscussionPaperforWednesday

ShiZ,GraberZT,BaumgartT,StoneHA,CohenE.(2018)CellMembranesResistFlow.Cell.175:1769-1779.

GrovesJT.(2019)MembraneMechanicsinLivingCells.DevCell.48:15-16.(abriefintro/reviewoftheShietal.paper)