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())

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fia

arnl)ruls euerquew :g 1 raldeq3 8 t9

THE LIPID BILAYER

nonpolar(hydrophobic)t a i l s

619

c H , - N * ( C H l ht -

CH,IoI

O : l ' - O -

I

o

rl

v

oz

,z

t lCH., CH.t ' l '9H, 9H,l l

C H , C H ,t - l ^C H . C H ,t ' l '9H, 9H,t l

C H , C H ,t - l9H, 9H,! , , 1 , , c , s - d o u b l e\ " '

" k b o n d

Ic H r

Figure 10-2 The parts of a phosphoglyceride molecule. This example is a phosphatidylchol ine,

represented (A) schematicai ly, (Bi by; iormula, (C) as a space-f i l l ing model, and (D) as a symbol ' The kink

result ing from the cis-double bond is exaggerated for emphasis.

CHOLINE

PHOSPHATE

IGLYCEROL

t ll l

1 2

CH:

o

C H rI\I

C H rI

Q H zIoI

, P -IoI

CHz

r i \ L \\ ? lCHI

C HIoI

f : P-IoI

H - C H

H

O H O Ht l

HC-CH-CH]l l n$H NHpl l 'CHI,l. | '

= ':.{'::. ' ?I ' q '

i > .: E i l

.,$

. . . .

-CH

IN HII

fz-

FF

! J = =

n A r . \ O

U U U v

F F F T _

[ d L L

C H :

-( ,o:

@ N H rI

fn'fn'ol^

O:P-O i l

IoI

CHr -CH-CHrt - lt l

oot lt l

- - 6 4 - 6

J J

U U

> >r -L U

phosphat idylethanolamine phosphat idylser ine

(A) (B)

Figure 10-3 Four major phospholipids in mammalian plasma membranes. Different head groups are represented by dif ferent colors in the

,y,"nbolr. Th. l ipid molecules shown in (A-C) are phosphoglycerides, which are derived from glycerol. The molecule in (D) is sphingomyelin,

which is derived from sphingosine (E) and is therefore a sfhingol ipid. Note that only phosphatidylserine carr ies a net negative charge, the

importance of which we disiuss later; the other three are'elecir ical ly neutral at physiological pH, carrying one posit ive and one negative charge'

sphingosine

(E)

phosphat idylchol ine sphingomyel i n

(c) (D)

620 Chapter 10: Membrane Structure

. H

polar head group

r i g i dsteroid

nngstructure

C H r C H rC HI

9H,9n,CH:I

CH

C H : C H ,

nonpolarhydrocarbonta i l

(B)(A)

In addition to phospholipids, the lipid bilayers in many cell membranescontain cholesterol and glycoliplds. Eucaryotic plasma membranes containespecially large amounts of cholesterol (Figure l0-4)-up to one molecule forevery phospholipid molecule. cholesterol is a sterol. It contains a rigid ringstructure, to which is attached a single polar hydroxyl group and a short non-polar hydrocarbon chain. The cholesterol molecules oiienf themselves in thebilayer with their hydroxyl group close to the polar head groups of adjacentphospholipid molecules (Figure r0-5).

Phospholipids Spontaneously Form Bilayers

The shape and amphiphilic nature of the phospholipid molecules cause them toform bilayers spontaneously in aqueous environments. As discussed in chapter2, hydrophilic molecules dissolve readily in water because they contain chargedgroups or uncharged polar groups that can form either favorable electrostiticinteractions or hydrogen bonds with water molecules. Hydrophobic molecules,by contrast, are insoluble in water because all, or almosi all, of their atoms are

The hydrophobic and hydrophilic regions of lipid molecules behave in the

Being cylindrical, phospholipid molecules spontaneously form bilayers inaqueous environments. In this energetically most favorable arrangement, thehydrophilic heads face the water at each surface of the bilayer, and thehydrophobic tails are shielded from the water in the interior. The same forcesthat-drive phospholipids to form bilayers also provide a self-healing property. Asmall tear in the bilayer creates a free edge with water; because thii is energLti-cally unfavorable, the lipids tend to rearrange spontaneously to eliminate the freeedge. (In eucaryotic plasma membranes, the fusion of lntracellular vesiclesrepairs larger tears.) The prohibition offree edges has a profound consequence:the only way for a bilayer to avoid having edges is by closing in on itself and form-ing a sealed compartment (Figure r0-8). This remarkable behavior, fundamental

Ec

Figure 10-4 The structure of cholesterol.Cholesterol is represented (A) by aformula, (B) by a schematic drawing, and(C) as a space-f i l l ing model.

il:-I t

4

Figure 10-5 Cholesterol in a l ipidbi layer. Schematic drawing of acholesterol molecule interacting with twophospholipid molecules in onemonolayer of a l ipid bi layer.

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arnlrn.tls eueJquary :0 t JaldeqJzz9

THE LIPID BILAYER 623

la teral d i f fus ion

rotation

\L.. . ,I flrp-Trop

| (rarelY occurs)

tI

I

{ lex ion

acid ta i ls

l ip id head groups

water molecules

Figure 10-1 1 The mobil ity of phospholipid molecules in an artif icial l ipid bila > Starting with

a model of 100 phosphatidylcholine molecules arranged in a regular bilayer, a c lculated theposition of every atom after 300 picoseconds of simulated time. From these theoretical calculations (taking

weeks of processor time in 1995), a model of the l ipid bilayer emerges that accounts for almost all of themeasurable properties of a synthetic l ipid bilayer, such as its thickness, numberof l ipid molecules per

membrane area, depth of water penetration, and unevenness of the two surfaces. Note that the tails in one

monolayer can interact with those in the other monolayer, if the tails are long enough. (B) The differentmotions of a lipid molecule in a bilayer. (A, based on 5.W. Chiu et al., Biophys. J.69:1230-1245, 1995. Withpermission from the Biophysical Society.)

two-dimensional rigid crystalline (or gel) state at a characteristic freezing point.

This change of state is called a phase transition, and the temperature at which it

occurs is lower (that is, the membrane becomes more difficult to freeze) if the

hydrocarbon chains are short or have double bonds. A shorter chain length

reduces the tendency of the hydrocarbon tails to interact with one another, in

both the same and opposite monolayer, and cls-double bonds produce kinks in

the hydrocarbon chains that make them more difficult to pack together, so that

the membrane remains fluid at lower temperatures (FigUre f0-f2). Bacteria,

yeasts, and other organisms whose temperature fluctuates with that of their

environment adjust the fatty acid composition of their membrane lipids to

maintain a relatively constant fluidity. As the temperature falls, for instance, the

cells of those organisms synthesize fatty acids with more cls-double bonds, and

they avoid the decrease in bilayer fluidity that would otherwise result from the

temperature drop.cholesterol modulates the properties of lipid bilayers. lvhen mixed with

phospholipids, it enhances the permeability-barrier properties of the lipid

bilayer. It inserts into the bilayer with its hydroryl group close to the polar head

groups of the phospholipids, so that its rigid, platelike steroid rings interact

with-and partly immobilize-those regions of the hydrocarbon chains closest

to the polar head groups (see Figure 10-5). By decreasing the mobility of the first

saturatedhydrocarbon chains

Figure 10-12 The influence of crs-double bonds in hydrocarbon chains.The double bonds make it more difficultto pack the chains together, therebymaking the l ipid bi layer more dif f icult tofreeze. In addition, because thehydrocarbon chains of unsaturated lipids

are more spread apart, l ipid bi layerscontaining them are thinner than bi layersformed exclusively from saturated lipids.

unsatu ratedhydrocarbon chains

with crs-double bonds

624 Chapter 10: Membrane Structure

Table 10-1 Approximate Lipid compositions of Different cell Membranes

CholesterolPhosphatidylethanolami nePhosphatidylserinePhosphatidylcholineSphingomyelinGlycolipidsOthers

3282440Irace23

few cH2 groups of the hydrocarbon chains of the phospholipid molecules,cholesterol makes the lipid bilayer less deformable in thiJregion and therebydecreases the permeability of the bilayer to small water-soluble molecules.Although cholesterol tightens the packing of the lipids in a bilayer, it does notmake membranes any less fluid. At the high concentrations found in mosteucaryotic plasma membranes, cholesterol also prevents the hydrocarbonchains from coming together and crystallizing.

- Table l0-l compares the lipid compositions of several biorogical mem-branes. Note that bacterial plasma membranes are often composed of one maintype of phospholipid and contain no cholesterol; their mechanical stability isenhanced by an overlying cell wall (see Figure ll-lg). In archaea, lipids usuallycontain 20-25-carbon-long prenyl chains instead of fatty acids, prenyl and fattyacid chains are similarly hydrophobic and flexible (see Figure ro-2op). rnus, lipidbilayers can be built from molecules with similar features but different molecu-lar designs. The plasma membranes of most eucaryotic cells are more varied thanthose of procaryotes and archaea, not only in containing large amounts ofcholesterol but also in containing a mixture of different phospholipids.

Analysis of membrane lipids by mass spectrometry has revealed that thelipid composition of a typicai cell membrane is much more complex than origi-nally thought. According to these studies, membranes are .omposed of a bewil-dering variery of 500-1000 different lipid species. \A/hile some of this complexityreflects the combinatorial variation in head groups, hydrocarbon chain lengths,and desaturation of the major phospholipid classes, membranes also containmany structurally distinct minor lipids, at least some of which have importantfunctions. TJee inositol phosphotipids, for example, are present in small quanti-ties but have crucial functions in guiding membrane traffic and in cell signaling(discussed in chapters 13 and 15, respectively). Their local synthesis anddestruction are regulated by a large number of enzymes, which create both smallintracellular signaling molecules and lipid docking sites on membranes thatrecruit specific proteins from the cytosol, as we discuss later.

Despite Their Fluidity, Lipid Bilayers Can Form Domains ofDifferent Compositions

Becausea lipid bilayer is a two-dimensional fluid, we might expect most types oflipid molecules in it to be randomly distributed in their o-wn monolayer. The vanderwaals attractive forces between neighboring hydrocarbon tails are not selec-tive enough to hold groups of phospholipid molecules together. with certainlipid mixtures, however, different lipids can come together iransiently, creatinga dynamic patchwork of different domains. In syntheiic lipid bilayerr composedof phosphatidylcholine, sphingomyelin, and cholesterol, van der waals forcesbetween the long and saturated hydrocarbon chains of the sphingomyelinmolecules can be just strong enough to hold the adjacent moleiuleslogethertransiently (Figure f 0-f 3).

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