An Introduction to Biological Membranes: From Bilayers to Rafts

364 Pages·9.321 MB·English

by  Stillwell W.

AN INTRODUCTION TO
BIOLOGICAL MEMBRANES
From Bilayers to Rafts
W S
ILLIAM TILLWELL
ProfessorEmeritusofBiology
IndianaUniversity
PurdueUniversity
Indianapolis
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Dedication
ThisbookisdedicatedtomywifePenelopewhohastoleratedmealltheseyears,myson
Max,my daughterJessica, andCosmo, thebrainsof the operation.
Preface
Virtually all biological processes are in book. While these multi-authored books
some fashion involved with membranes. have their place in membrane studies, they
However,despitetheirunquestionedimpor- are essentially a non-cohesive collection of
tance, many aspects of complex membrane looselyrelatedreviewarticlesthatarewritten
structure and function remain unresolved. by experts from very different backgrounds
Oftennotonlyaretheanswersnotavailable, and writing styles. As a result they are
but even formulating the appropriate ques- comprehensive, but very hard to read. In
tions is difficult. A single membrane is sharp contrast, excellent general discussions
composedofhundredsofproteinsandthou- covering membranes can now be found
sandsoflipids,allinconstantflux.Method- in very well written chapters in almost all
ologiestostudymembranesmustspantime current biochemistry, cell and molecular
and size domains that range over a million biology, and physiology textbooks. These
fold! A good case can be made that under- brief chapters are of necessity too abbrevi-
standing membranes will be the next great atedtoadequatelycoverafieldasexpansive
frontier inthe life sciences. asmembranes.Themulti-authoredcompen-
From the inception, it became obvious to diums are too detailed while the chapters
methattryingtowriteabookonmembranes fromgeneraltextbookslacksufficientdetail.
is a near hopeless endeavor. No-one can Between the extremes of edited compen-
possibly be an expert in all aspects of diums and general textbook chapters are
membranescience.Membranestudiesrange a smaller number of general membrane
fromstructuralandtheoreticalbiophysicsat books that have the advantage of being
one extreme to nutritional, cell biology, and writtenbyasingle(oratmostafew)authors.
membrane metabolic studies at the other. AnIntroductiontoBiologicalMembranes:From
Bridging the two extremes are countless Bilayers to Rafts is such a book. This book
highlytechnicalmethodologiesthatarediffi- is an attempt to write a broad textbook
cult to explain without getting hopelessly covering many aspects of membrane struc-
boggeddownintechnicalminutia.Choosing ture/function that bridges membrane
whatshouldbeincludedandwhatexcluded biophysics and cell biology. It was my basic
fromthisbookreflectsmypersonal40years contention that it is not necessary to under-
ofresearchexperienceonthebiophysicsand stand the intricacies of NMR, single particle
biochemistry of model membrane systems. tracking, X-ray crystallography and so on,
Throughtheyearstherehavebeenalarge to appreciate the contributions that these
number of books written about membranes. techniqueshavemadetomembranestudies.
Most of these have been multi-authored, Thebookprimarilytargetsadvancedunder-
highlytechnicalcompendiumsthatareessen- graduatesandbeginninggraduatestudents.
tially“preachingtothechoir”.Theyareinde- However, even membranologists with
cipherable to anyone who is not already an a good knowledge of contributions by their
expert in the narrow topic covered in the contemporaries often have very limited
ix
x
PREFACE
knowledgeoffundamentalcontributionsby Luckey, M. 2008. Membrane Structural
earlymembranepioneers,arecurringtheme Biology. With Biochemical and
of this book. The appendix to this book is BiophysicalFoundations. Cambridge
a time line of 100 of the most important University Press,New York, NY,
discoveries in membrane science dating 332 pp.
from ~540 BCto present. Mouritsen,O.G.2005. Life as aMatterof
In the process of cleaning out my office Fat. The EmergingScienceof
beforefadingintoretirementin2010,Ifound Lipidomics. Springer, Berlin,
that I had accumulated about 60 membrane Heidelberg,276pp.
books, and this is only a fraction of what is Jones, M.N. and Chapman, D.1995.
available. For 30 years I taught a beginning Micelles, Monolayers and
graduate level course entitled Biological Biomembranes. John Wiley and Sons,
Membranes. For most of those years I could New York. 252 pp.
not find a suitable textbook for the course. Yeagle,P.L.1993.TheMembranesofCells,
In 1988 Robert B. Gennis published his 2nd Edition.Academic Press,
book Biomembranes: Molecular Structure and New York. 349 pp.
Function. To this day I consider Gennis’ Jain,M.K.1988.IntroductiontoBiological
book to be the best membrane structure Membranes,2ndEdition.JohnWiley&
book ever written and for about 10 years I Sons, NewYork. 423 pp.
adopted this book for my course. Unfortu- Finean, J.B.,Coleman, R. andMichell,
nately, after 25 years, a second edition of R.H. 1984.MembranesandTheir
thisbookhasyettobepublished.Something Cellular Functions, 3rdEd. Blackwell
is needed to fill this gap. From my perspec- Scientific Publications, Oxford,
tive, the new book should be a single- New York. 227 pp.
authored, broad book that covers many Malhotra,S.K. 1983. The Plasma
aspectsofmembranestructureandfunction Membrane. John Wiley andSons,
withoutgettinglostinunnecessarydetailse New York. 209 pp.
inotherwords,‘membranebiophysicslight’. Houslay,M.D. andStanley, K.K.1982.
ItisclearthateachtopiccoveredinAnIntro- Dynamicsof Biological Membranes:
ductiontoBiologicalMembranes:FromBilayers Influenceon Synthesis, Structureand
to Rafts could be greatly expanded, but this Function. John Wiley &Sons,
will have to wait for anotherday. New York. 330 pp.
Through the years other single-authored
general membrane books have appeared, William Stillwell
eachofwhichhasitsadvantagesanddisad-
Sand Key, Florida
vantages.Afew examplesarelisted below:
January,2013
Gennis,R.B.1988.Biomembranes:
MolecularStructureandFunction.
Springer-Verlag.NewYork,NY.533pp.
C H A P T E R
1
Introduction to Biological Membranes
O U T L I N E
A. Whatisa Biological Membrane? 1 Mitochondria 7
B. General MembraneFunctions 3 D.Size of Domains 8
Can we see amembrane? 9
C. Eukaryote Cell Structure 4
Can we see acell? 9
EndomembraneSystem 4
Whatcanyouseewithalight
Plasma Membrane 4
microscope? 9
Nuclear Envelope (Membrane) 6
EndoplasmicReticulum(ER) 7 E. Basic Composition of Membranes 10
Golgi Apparatus 7
Summary 11
Lysosome 7
Peroxisome 7 References 11
A. WHAT IS A BIOLOGICAL MEMBRANE?
TheAmericanHeritageDictionarydefinesamembraneas‘athinpliablelayerofplantor
animal tissue covering or separating structures or organs.’ The impression this description
leaves is one of the plastic wrap covering a hamburger. By this definition, membranes are
static, tough, impenetrable, and visible. Yet, nothing could be farther from the truth. The
entire concept of dynamic behavior is missing from this definition, yet dynamics is what
makes membranesbothessentialfor life and sodifficult to study.
Ifwecouldsomehowinstantaneouslyfreezeamembraneandlearnthecompositionand
locationofeachofthecountlessnumbersofmoleculescomprisingthemembrane,andthen
instantly return the membrane back to its original unfrozen state for a microsecond before
re-freezing, we would find that the membrane had substantially changed while unfrozen.
Although the molecular composition would remain the same over this short time, the
AnIntroductiontoBiologicalMembranes
http://dx.doi.org/10.1016/B978-0-444-52153-8.00001-5 1 Copyright(cid:1)2013ElsevierB.V.Allrightsreserved.
2
1. INTRODUCTIONTOBIOLOGICALMEMBRANES
molecular locations and interrelationships would be altered. Therefore membranes must
have both static and dynamic components. While static describes what is there, dynamics
describeshow thecomponents interact to generatebiological function.
Every cell in the human body is a tightly packed package of countless membranes. The
humanbody iscomposedof~63 trillion cells(6.3 (cid:1)1013cells), eachofwhich isverysmall.
Forexample,atypicallivercellwouldhavetobe5Xlargertobeseenasaspeckbysomeone
with excellent vision (it is microscopic). Each liver cell has countless numbers of internal
membranes.Ifyoucouldsomehowopenonesinglelivercellandremovealloftheinternal
membranesandsewthemtogetherintoaquilt,thequiltwouldcover~840acres,thesizeof
New York’s Central Park! And that is from one single cell. Therefore, there are enough
membranes in ahuman body (6.3(cid:1) 1013cells) to cover theearthmillions of times over!
AlllifeonEarthisfarmoresimilarthanitisdifferent.Livingorganismsshareanumberof
essential biochemical properties, collectively termed the ‘thread of life’. Included in these
essentialpropertiesisownershipofasurroundingplasmamembranethatseparatesthecell’s
interiorfromitsexternalenvironment.ItislikelythatalllivingthingsinhabitingplanetEarth
today arose from a single common ancestor more than 3.5 billion years ago. The first cell
probably contained minimally a primitive catalyst (a pre-protein), a primitive information
storage system (a pre-nucleic acid), a source of carbon (perhaps a primitive carbohydrate)
and this mixture had to be surrounded by a primitive plasma membrane that was likely
made of polar lipids. Membranes were therefore an essential component of every cell that
isalive today orhas ever been alive.
With 3.5 billion years of biological evolution, the complexity of membranes in cells has
greatly expanded from that of a simple surrounding plasma membrane to where they
now occupy a large portion of a eukaryote’s interior space. An electron microscopic
picture of a ‘typical’ eukaryotic (liver) cell is shown in Figure 1.1 [1]. It is evident from
the complexity of this micrograph that identifying, isolating, and studying membranes
will be a difficult task.
FIGURE1.1 Transmissionelectronmicrographofalivercell,a‘typical’cell[1].
3
B. GENERALMEMBRANEFUNCTIONS
B. GENERAL MEMBRANE FUNCTIONS
Itisnowgenerallyagreedthatbiologicalmembranesareprobablysomehowinvolvedin
allcellularactivities.Themostobviousfunctionofanymembraneisseparatingtwoaqueous
compartments. For the plasma membrane this involvesseparation of thecellcontents from
the very different extra-cellular environment. Membranes are therefore responsible for
containment, ultimately delineating the cell. Separation, however, cannot be absolute, as
thecellmustbeabletotakeupessentialnutrients,gases,andsolutesfromtheexterior,while
simultaneously removing toxic waste products from the interior. A biological membrane
therefore must be selectively permeable, possessing the ability to distinguish many chemi-
cally different solutes and knowing in which direction to redistribute them. Biological
membranesmustthereforehouseavarietyofspecific,vectorialtransportsystems(discussed
in Chapter14).
Acharacteristicofalllivingcellsistheestablishmentandmaintenanceoftrans-membrane
gradientsofallsolutes.Ofparticularinterestarelargeiongradientstypicallyassociatedwith
theplasmamembrane.Table1.1isacomparisonofthemeanconcentrationofselectedions
insideandoutsideatypicalmammaliancell,andthemagnitudeofeachgradient.Tomain-
tain gradients of this size, efficient energy-dependent transport systems must be employed
(discussedinChapter14).Directionaltrans-membranestructureisrequiredtogeneratethese
ion gradients.
Inadditiontotrans-membranestructure,itisnowbelievedthatbiologicalmembranesare
composedofcountlessnumbersofverysmall,transient,laterallipidmicrodomains.Eachof
thesedomainsisproposedtohaveadifferentlipidandresidentproteincomposition.Thus
the activity of any membrane must reflect the sum of the activities of its many specific
domains. One type of lipid microdomain, termed a ‘lipid raft’, has received a lot of recent
attentionasitisreputedtobeinvolvedinavarietyofimportantcellsignalingevents.Ifthe
lipid raft story (discussed in Chapter 8) holds up, this new paradigm for membrane struc-
ture/functionmayserveasamodelforothertypesofasyetundiscoverednon-raftdomains.
Eachofthesedomainsmightthensupportadifferentcollectionofrelatedbiochemicalactiv-
ities. Therefore, membranes have both trans-membrane and lateral structures that are just
beginningto be understood.
Allmembranespossessanextremewatergradientacrosstheirverythin(~5nm)structure.
In the membrane aqueous bathing solution water concentration is ~55.5 M water in water
(1,000gofwaterperliterdividedby18,themolecularweightofwater),whilethemembrane
TABLE1.1 Trans-membraneIonGradientsofa‘Typical’MammalianCell.
Ion Inside Outside Gradient
þ
Na 10mM 140mM 14-fold
þ
K 140mM 4mM 35-fold
Ca2þ 1.0mM 1.0mM 1,000-fold
(cid:3)
Cl 100mM 4.0mM 25-fold
4
1. INTRODUCTIONTOBIOLOGICALMEMBRANES
interiorisquitedry(<1mMwater).Theaqueousinterfaceprovidesachargedorpolarphys-
icalsurfacetohelparrangerelatedfunctionalenzymes,knownaspathways,inoneplanefor
increased efficiency. In contrast, the dry interior provides an environment for dehydration
reactions. Both the aqueous interface and dry interior are responsible for maintaining the
properconformation of membrane proteins(discussedin Chapter6).
Inadditiontotransport,biologicalmembranesarealsothesiteofmanyotherbiochemical
orphysiologicalprocessesincluding:inter-cellularcommunication,cellecellrecognitionand
adhesion,cellidentityandantigenicity,regulation(residenthomeofmanyreceptors),intra-
cellularsignaling, andsomeenergytransductionevents.
C. EUKARYOTE CELL STRUCTURE
While the plasma (cell) membrane defines cell boundaries, internal membranes define
a variety of cell organelles. In eukaryotes, the internal membranes also separate very
different internal aqueous chambers resulting in compartmentation into membrane-
bordered packets called organelles. Each organelle supports different sets of biological
functions. Figure 1.2 is a cartoon depiction of a ‘typical’ animal (eukaryote) cell [2]. All
oftheimportantmembrane-boundorganellesaredepicted.Throughoutthisbook,specific
examples demonstrating aspects of membrane structure or function will be selected from
these organelle types. Below is a very brief description of the major cellular membranes.
Moredetaileddescriptionscanbereadilyfoundinmanycellbiology[3e6],andbiochem-
istry [7,8] textbooks.
Endomembrane System
Withtheexceptionofmitochondria,peroxisomesand,inplants,chloroplasts,theintracel-
lular membranes are suspended together in the cytoplasm where they form an intercon-
nected complex. Although membrane types are unique and can be separated from one
another, all are related structurally, chemically, functionally, and developmentally. This
strong inter-relationship is referred to as the ‘endomembrane system’. The endomembrane
system divides the cell into many compartments, primarily organelles, which are distinct
yet interconnected. The connected membranes include the nuclear envelope, the rough
and smooth endoplasmic reticulum, the Golgi apparatus, lysosomes, vacuoles, many types
of small vesicles, and the plasma membrane (Figure 1.3) [9]. Transport back and forth
betweenthesevariousmembranesandcompartmentsiscontinuousandunderstrictregula-
tion [10]. The endomembrane system isthe foundationof cell trafficking.
Plasma Membrane
All cells are surrounded by a plasma membrane (PM) that separates the cell contents
from the rest of the world [11]. The PM is the most dynamic and busiest of all cellular
membranes and more is known about the PM than any other membrane. The majority of
examples described in this book were obtained from PM studies. The PM defines the cell’s