CHAPTER 11

MEMBRANE STRUCTURE
 2004 Garland Science Publishing

The Lipid Bilayer

11-1 For each of the following sentences, fill in the blanks with the best word or phrase
selected from the list below. Not all words or phrases will be used; each word or phrase
should be used only once.

The specialized functions of different membranes are largely determined

by the __________________ they contain. Membrane lipids are
__________________ molecules, composed of a hydrophilic portion and
a hydrophobic portion. All cell membranes have the same
__________________ structure, with the __________________ of the
phospholipids facing into the interior of the membrane and the
__________________ on the outside. The most common lipids in most
cell membranes are the __________________. The head group of a
glycolipid is composed of __________________.

amphipathic hydrophobic phosphatidylserine

cholesterol lipid bilayer phospholipids
fatty acid tails lipid monolayer proteins
glycolipids lipids sterols
hydrophilic head groups phosphatidylcholine sugars

11-2 Which of the following membrane lipids does not contain a fatty acid tail?
(a) Phosphatidylcholine
(b) A glycolipid
(c) Phosphatidylserine
(d) Sphingomyelin
(e) Cholesterol

11-3 Which of the following statements regarding lipid membranes is TRUE?

(a) Phospholipids will spontaneously form liposomes in nonpolar solvents.
(b) In eucaryotes, all membrane-enclosed organelles are surrounded by one lipid
bilayer.
(c) Membrane lipids diffuse within the plane of the membrane.
(d) Membrane lipids frequently flip-flop between one monolayer and the other.
(e) The preferred form of a lipid bilayer in water is a flat sheet with exposed edges.

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11-4 A bacterium is suddenly expelled from a warm human intestine into the cold world
outside. Which of the following adjustments might the bacterium make to maintain the
same level of membrane fluidity?
(a) Increase the length of the hydrocarbon tails in its membrane phospholipids.
(b) Increase the proportion of unsaturated hydrocarbon tails in its membrane
phospholipids.
(c) Increase the proportion of hydrocarbon tails with no double bonds in its
membrane phospholipids.
(d) Decrease the amount of cholesterol in the membrane.
(e) Decrease the amount of glycolipids in the membrane.

11-5 Which of the following statements regarding the fatty acid tails of phospholipids is
FALSE?
(a) Phospholipids with unsaturated tails make the bilayer more fluid because the tails
contain fewer hydrogen atoms and thus form fewer hydrogen bonds with each
other.
(b) Saturated phospholipid tails pack more tightly against each other than do
unsaturated tails.
(c) Most membrane phospholipids have one fully saturated tail.
(d) Phospholipid tails in a membrane can interact with each other via van der Waals
interactions.
(e) Fatty acid tails vary in length.

11-6 New membrane synthesis occurs by

(a) the spontaneous aggregation of free phospholipids into a new bilayer in the
aqueous environment of the cell.
(b) incorporation of phospholipids into both faces of a preexisting membrane by
enzymes attached to each face.
(c) incorporation of phospholipids into one face of a preexisting membrane and their
random redistribution to both faces by flippases.
(d) incorporation of phospholipids into one face of a preexisting membrane and their
specific redistribution by flippases.

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11-7 Three phospholipids X, Y, and Z are distributed in the plasma membrane as indicated in
Figure Q11-7. For which of these phospholipids does a flippase probably exist?

Figure Q11-7

(a) X only
(b) Z only
(c) X and Y
(d) Y and Z
(e) X and Z

11-8 Where does most new membrane synthesis take place in a eucaryotic cell?
(a) In the Golgi apparatus
(b) In the endoplasmic reticulum
(c) In the plasma membrane
(d) In the mitochondria
(e) On ribosomes

11-9 A small membrane vesicle containing a transmembrane protein is shown below. Assume
this membrane vesicle is in the cytoplasm of a cell.

Figure Q11-9

A. Label the cytosolic and non-cytosolic faces of the membrane vesicle. This
membrane vesicle will undergo fusion with the plasma membrane.
B. Sketch the plasma membrane after vesicle fusion, indicating the new location of
the vesicle membrane and the transmembrane protein carried by the membrane
vesicle.
C. On your drawing for B, label the original cytosolic and noncytosolic faces of the
vesicle membranes as it resides in the plasma membrane. Also label the
extracellular space and the cytosol. Indicate the amino and carboxyl terminus of
the inserted transmembrane protein.

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11-10 Why are glycolipids found on the extracellular, but not the cytoplasmic, surface of the
plasma membrane?
(a) Flippases transport them from the cytosolic face.
(b) The enzymes that produce them are present only on the extracellular surface of
the plasma membrane.
(c) The enzymes that add the sugar groups are confined to the inside of the
endoplasmic reticulum and the Golgi apparatus.
(d) The oligosaccharides on glycolipids are cleaved off by enzymes found only in the
cytosol.
(e) They flip spontaneously, after incorporation, due to the hydrophilic sugar head
groups.

Membrane Proteins

11-11 A group of membrane proteins, which can be extracted only from membranes using
detergents, are all found to have a similar amino acid sequence at their carboxyl terminus:
-KKKKKXXC (where K stands for lysine, X stands for any amino acid, and C stands for
cysteine). This sequence is essential for their attachment to the membrane. What is the
most likely way in which the carboxyl-terminal sequence attaches these proteins to the
membrane?
(a) The cysteine residue is covalently attached to a membrane lipid.
(b) The peptide spans the membrane as an α helix.
(c) The peptide spans the membrane as part of a β sheet.
(d) The positively charged lysine residues interact with an acidic integral membrane
protein.

11-12 A strain of bacteria secretes a toxin that can lyse human red blood cells. You are able to
partially purify the toxin and find that it is a small protein. Furthermore, the toxin is
capable of rendering liposomes made of pure phospholipids permeable to many different
ions. What type of protein is the bacterial toxin likely to be?
(a) A flippase
(b) A β-barrel protein
(c) A protease
(d) A protein containing a single hydrophobic α helix.
(e) An enzyme that adds carbohydrate groups to lipids.

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11-13 For each of the following sentences, fill in the blanks with the best word or phrase
selected from the list below. Not all words or phrases will be used; each word or phrase
should be used only once.

There are several ways that membrane proteins can associate with the cell
membrane. Membrane proteins that extend through the lipid bilayer are
called __________________ proteins and have __________________
regions that are exposed to the interior of the bilayer. On the other hand,
membrane-associated proteins do not span the bilayer and instead
associate with the membrane through an α-helix that is
__________________. Other proteins are __________________ attached
to lipid molecules that are inserted in the membrane.
__________________ membrane proteins are linked to the membrane
through noncovalent interactions with other membrane-bound proteins.

amphipathic hydrophilic noncovalently

cortical hydrophobic peripheral
covalently integral transmembrane
detergent micelle unfolded

11-14 Which of the following statements regarding membrane proteins is FALSE?

(a) Integral membrane proteins often precipitate (form insoluble aggregates) in
aqueous solutions lacking detergents.
(b) Some hydrophobic amino acids in membrane proteins are not in contact with the
lipid bilayer.
(c) Peripheral membrane proteins can be dissociated from membranes using a gentle
detergent.
(d) Strong detergents can completely unfold both membrane and nonmembrane
proteins.
(e) In transmembrane proteins that form an aqueous pore through the membrane, the
pore is lined with hydrophobic amino acid side chains.

11-15 Proteins often span the plasma membrane as an α- helix. If it takes 20 amino acids to
span a lipid bilayer, which of the three 20-amino acid sequences listed below is the most
likely candidate for such a transmembrane segment? Explain your choice.
(a) IALIVFGVFAGVIGGILLIS
(b) KITPVVKHKHDKIDTPLLIR
(c) DTYYYRRREADDDDDLLISD

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11-16 Proteins that form a ß-barrel pore in the membrane have several ß-strands that span the
membrane. The amino acid side chains facing the inside of the pore would be
hydrophilic whereas the amino acid side chains facing the lipid bilayer would be
hydrophobic. Which of the three 10-amino acid sequences listed below is the most likely
candidate for a transmembrane ß-strand in a ß-barrel protein? Explain your choice.
(a) ADFKLSVELT
(b) AFLVLDKSET
(c) AFDKLVSELT

11-17 Which of the following functions does the cell cortex perform?
(a) It influences the passage of small molecules into and out of the cell.
(b) It allows cells to change shape and to move.
(c) It lubricates the cell.
(d) It restricts the movement of certain proteins in the lipid bilayer.
(e) It supports and strengthens the membrane.

11-18 You have isolated two mutants of a normally pear-shaped microorganism that have lost
their distinctive shape and are now round. One of the mutants has a defect in a protein
you call A and the other has a defect in a protein you call B. You grind up each type of
mutant cell and normal cells separately and separate the plasma membranes from the
cytoplasm. You then wash the membrane fraction with a low concentration of urea
(which will unfold proteins and disrupt their ability to interact with other proteins) and
centrifuge the mixture. The membranes and their constituent proteins form a pellet while
the proteins liberated from the membranes by the urea wash remain in the supernatant.
When you check each of the factions for the presence of A or B, you obtain the results
given below.

First cell extract After urea wash and centrifugation

Membrane Cytosol Membrane Supernatant
Normal cells A and B no A or B A B
Mutant A A B A no A or B
Mutant B A B A no A or B

Which of the following statements are consistent with your results?

(a) Protein A is an integral membrane protein that interacts with B, a peripheral
membrane protein that is part of the cell cortex.
(b) Protein B is an integral membrane protein that interacts with A, a peripheral
membrane protein that is part of the cell cortex.
(c) Proteins A and B are both integral membrane proteins.
(d) The mutation in A affects its ability to interact with B.
(e) The mutation in A affects its ability to interact with the membrane.

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11-19 Detergents and phospholipids are both amphipathic molecules. However, when exposed
to water, detergents aggregate into small clusters called micelles while phospholipids
form closed spherical liposomes. Explain what the difference is between the structure of
a detergent compared to the structure of a phospholipid that causes detergents to form
micelles instead of liposomes.

11-20 Diversity among the oligosaccharide chains found in the carbohydrate coating of the cell
surface can be achieved in which of the following ways?
(a) Varying the types of sugar monomers used
(b) Varying the types of linkages between sugars
(c) Varying the number of monomers in the chain
(d) Varying the number of branches in the chain
(e) All of the above

11-21 Which of the following statements about the carbohydrate coating of the cell surface is
FALSE?
(a) It is not usually found on the cytosolic side of the membrane.
(b) It can play a role in cell-cell adhesion.
(c) The arrangement of the oligosaccharide side chains are highly ordered, much like
the peptide bonds of a polypeptide chain.
(d) Specific oligosaccharides can be involved in cell-cell recognition.
(e) It can protect the cell surface from mechanical and chemical damage.

11-22 Cell membranes are fluid and thus proteins can diffuse laterally within the lipid bilayer.
However, sometimes the cell needs to localize proteins to a particular membrane domain.
Name three mechanisms a cell can use to restrict a protein to a particular place in the cell
membrane.

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How We Know: Measuring Membrane Flow

11-23 Fluorescence recovery after photobleaching (FRAP) is a technique that allows

visualization of diffusion within the membrane. You set out to perform FRAP using four
different samples of cells. In sample 1, you have fluorescently labeled a phospholipid. In
samples 2, 3, and 4 you have fluorescently labeled membrane proteins X, Y, and Z,
respectively. You photobleach an area of the membrane in each sample and record the
rate of recovery of fluorescence. The data you obtain are shown in the graphs below:

Figure Q11-23

A. Using the data from these graphs, list the proteins in order of their ability to
diffuse in the membrane, from fastest to slowest.
B. Given the data on the graphs above, is the following statement a good hypothesis:
protein X and protein Z are always present in the cell as part of the same protein
complex? Explain your answer.

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11-24 You perform single-particle tracking (SPT) experiments on three proteins, A, B, and C,
and obtain the following pathways:

Figure Q11-24

A. Which protein displays a pattern of motion similar to a protein that is anchored to

the cytoskeleton?
B. If you were to find a cell containing a membrane where 10% of its membrane
proteins were anchored to the cytoskeleton, how do you think this would affect
the fluidity of the lipids in the membrane?

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Answers

11-1 The specialized functions of different membranes are largely determined by the proteins
they contain. Membrane lipids are amphipathic molecules, composed of a hydrophilic
portion and a hydrophobic portion. All cell membranes have the same lipid bilayer
structure, with the fatty acid tails of the phospholipids facing into the interior of the
membrane and the hydrophilic head groups on the outside. The most common lipids in
most cell membranes are the phospholipids. The head group of a glycolipid is composed
of sugars.

11-2 (e)

11-3 (c) The remaining answers are false. Phospholipids form bilayers only in polar
solvents. Nuclei and mitochondria are enclosed by two membranes. Membrane
lipids rarely flip-flop between one monolayer and the other. The preferred form
of a lipid bilayer in water is a closed sphere, so that the hydrophobic groups at
the edges of the bilayer can avoid contact with water.

11-4 Choice (b) is the correct answer. At colder temperatures, the membrane will be less fluid.
Hence, in order to maintain the status quo, the bacterium will have to take measures to
increase membrane fluidity. Increasing the length of the hydrocarbon tails (choice (a))
would decrease membrane fluidity, while decreasing the number of glycolipids (choice
(e)) would have little or no effect. Decreasing the proportion of fatty acid tails with no
double bonds (fully saturated) (choice (c)) would decrease membrane fluidity. Bacteria
do not have cholesterol (choice (d)).

11-5 (a) Unsaturated fatty acid tails do have fewer hydrogen atoms and do interact less
well with one another but not for the reason stated. The decrease in interaction is
due to a decrease in van der Waals interactions between the hydrocarbon tails
because they can pack less closely. Hydrocarbon chains cannot form hydrogen
bonds with each other.

11-6 (d)

11-7 (c) As phospholipids are initially inserted into the cytosolic face of the lipid bilayer,
flippases are required to move X and Y to the opposite face, as they cannot
spontaneously flip across the bilayer.

11-8 (b)

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11-9 A. See Figure A11-9A.

Figure A11-9A

B., C. See Figure A11-9B.

Figure A11-9B

11-10 (c)

11-11 (a) The peptide is extremely hydrophilic and is, therefore, unlikely to be inserted into
the lipid bilayer. It is also too short to span the membrane as an α-helix. Although
it is possible that the lysines interact with an acidic membrane protein, if such an
interaction were solely responsible for attaching the protein to the membrane, it
would not require a detergent to remove the protein, since ionic interactions are
disrupted by milder treatments such as salt washes and pH changes.

11-12 Choice (b) is the correct answer. Insertion of a pore-forming protein into the lipid bilayer
will have the effects noted by making the red blood cell unable to regulate its internal ion
composition. The type of protein most likely to form the sort of nonspecific pore
described is a β-barrel protein. Enabling membrane lipids to flip from one layer of the
bilayer to the other should not affect permeability (choice (a)). A protease would have no
effect on liposomes made of pure phospholipids (choice (c)). Proteins containing a single
hydrophobic α-helix would not form a channel through the membrane (choice (d)).
Addition of carbohydrate groups to lipids should not make the bilayer any more
permeable to ions (choice (e)).

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11-13 There are several ways that membrane proteins can associate with the cell membrane.
Membrane proteins that extend through the lipid bilayer are called transmembrane
proteins and have hydrophobic regions that are exposed to the interior of the bilayer. On
the other hand, membrane-associated proteins do not span the bilayer and instead
associate with the membrane through an α-helix that is amphipathic. Other proteins are
covalently attached to lipid molecules that are inserted in the membrane. Peripheral
membrane proteins are linked to the membrane through noncovalent interactions with
other membrane-bound proteins.

11-14 Choice (e) is the correct answer. In transmembrane proteins that form an aqueous pore
through the membrane, the pore is lined with hydrophilic amino acid side chains. The
other statements are all true. Integral membrane proteins often precipitate in aqueous
solutions because of their stretches of hydrophobic amino acids (choice (a)). Proteins
also contain hydrophobic amino acids in parts of the protein other than the membrane-
spanning region, for example, in the cores of their extracellular or cytoplasmic domains
(choice (b)). Peripheral membrane proteins are attached to the membrane by noncovalent
interactions with other membrane proteins, making their membrane association relatively
weak and thus disruptable by gentle detergents (choice (c)).

11-15 Choice (a) is the correct answer. When an α-helix traverses a lipid bilayer, the amino acid
side chains are exposed to the hydrophobic portion of the lipid bilayer and thus should
consist of nonpolar side chains. The sequence given in choice (a) contains nonpolar
amino acids. Choices (b) and (c) are inappropriate, as they both contain several
negatively and positively charged amino acids.

(Note that in addition, choice (b) contains two prolines, which would render this
sequence unable to form an α-helical structure and therefore lead to exposure of the
hydrogen-bonding moieties in the polypeptide background to the nonpolar environment
of the lipid bilayer.)

11-16 (a) In a β-sheet, the amino acid side chains project alternately above and below the
plane of the sheet. Therefore, every other amino acid side chain will face the
same side of the strand. If a β-sheet were part of a β-barrel pore, that would mean
that one side of the sheet would face the lipid bilayer while the other side would
face the hydrophilic pore. This would necessitate an alternation between
hydrophilic and hydrophobic amino acid side chains so that one side of the sheet
would be hydrophobic while the other side was hydrophilic. The amino acids in
choice (a) alternate between amino acids with nonpolar (hydrophobic) side chains
and amino acids with polar (hydrophilic) side chains.

11-17 (b), (d), and (e)

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11-18 (a), (d) The results from the extracts of normal cells show that protein A is an integral
protein that remains in the membrane through all the treatments, while protein B
is a peripheral protein that can be removed from the membrane by urea. In the cell
extracts from the mutants in A, the protein A still remains in the membrane, but
the B protein does not. This is consistent with the mutation in A affecting its
interaction with B. The same results are obtained when the B protein is mutant,
which is consistent with the idea that A and B interact. The loss of an interaction
between an integral membrane protein and a protein in the cortex would be more
likely to result in a change in cell shape than the loss of an interaction between an
integral membrane protein and a protein on the exterior of the cell.

11-19 A detergent has one hydrophobic tail while a phospholipid has two hydrophobic tails.
This difference is reflected in the geometry of the molecules, with detergent molecules
being shaped more like cones whereas phospholipids are more cylindrical. The cone-like
detergent molecules will aggregate into micelles, with the hydrophilic head group on the
outside and the hydrophobic tail group on the inside. On the other hand, the cylindrical
shape of a phospholipid means that when phospholipids aggregate, the formation of a
bilayer is most energetically favorable, with the hydrophobic tails on the inside of the
two-layered sheet and the hydrophilic heads facing the water molecules. However, it is
not energetically favorable for a phospholipid bilayer to exist as a sheet, because the
exposed free edges would lead to exposure of the hydrophobic tails to water. Therefore,
phospholipid bilayers spontaneously close to form spherical liposomes.

11-20 (e)

11-21 (c) The sugars in an oligosaccharide side chain attached to the cell surface can be
joined together in many different ways and in varied sequences.

11-22 Any combination of these four answers is acceptable:

1. The protein can be attached to the cell cortex inside the cell.
2. The protein can be attached to the extracellular matrix outside the cell.
3. The protein can be attached to other proteins on the surface of a different cell.
4. The protein can be restricted in its ability to diffuse by a diffusion barrier, such as
that set up by specialized junctional proteins at a tight junction.

11-23 A. X diffuses the fastest, followed by Z, with Y barely diffusing at all. (The faster
the recovery of fluorescence in the bleached area, the greater the diffusion
coefficient of the protein and the faster the protein diffuses.)
B. It is unlikely that X and Z are part of the same protein complex because then the
rate of diffusion of X and Z should be the same.

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11-24 A. Protein C displays the least amount of motion and therefore is the one most likely
to be tethered to the cytoskeleton.
B. The fluidity of the lipid bilayer should not be affected by the anchoring of
membrane proteins. The lipid molecules should still be able to flow around
anchored proteins much like water flows around rocks in a stream. (Note that the
fluidity of the lipid bilayer is affected by the degree of saturation found in the
hydrocarbon tails, the length of the hydrocarbon tails, and in animal cells, the
amount of cholesterol in the membrane.)

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