Lecs 4, 5:

Biological Membranes

Chapter 6

Detailed molecular model of the phospholipid bilayer

in a biological membrane.
1
J G Burr, 9/1/14

The current molecular model for the

structure of biological membranes: the
Singer-Nicholson fluid mosaic model.

Phospholipid bilayer

Membrane protein, traversing

the lipid bilayer. (Protein
iceberg, floating in a sea of
lipid.)

J G Burr, 9/1/14

Membranes are made of lipids and proteins.

Lets look first at lipids. Well talk about them in a
general way, before moving into their role in membranes.
A lipid is a water-insoluble hydrocarbon
The three major types of lipids found in cells are:
1) Fats

Found as droplets inside cells (food storage form)

2) Phospholipids

Form cell membranes

3) Cholesterol (and other cholesterol-related molecules

(eg, steroids)

Cholesterol strengthens cell membranes, and serves

as a precursor for steroid hormone synthesis

3
J G Burr, 9/1/14

Lets begin with fats.

Fats are formed by esterifying 3 fatty acid molecules with a

molecule of glycerol. (Remember your organic chemistry: an
alcohol (glycerol) reacts with an acid to form an ester)

Glycerol is
a 3-carbon
polyalcohol

The acidic carboxyl group is

sometimes referred to as an
acyl group
Fats are
sometimes called
triglycerides, or
triacylglycerol

4
J G Burr, 9/1/14

More about fatty acids:

Fatty acids are amphipathic molecules. That
means a water-soluble region and an insoluble region
are found in the same molecule. In a fatty acid, the
long hydrocarbon chain (the tail) is oily and
insoluble in water (hydrophobic), while the
carboxyl group (the head) is soluble in water
(hydrophilic).

Long, hydrophobic
hydrocarbon tail

Carboxyl group head

is hydrophilic

5
J G Burr, 9/1/14

Fatty acids form micelles:

When fatty acids are added to water, they spontaneously
form spherical structures called micelles, in which the
hydrocarbon tails are sequestered in the interior, away
from water, and the hydrophilic heads are on the surface,
able to hydrogen-bond with water. .

3-dimensional
representation
of a micelle:
6
J G Burr, 9/1/14

Fatty acids and other, similar, amphipathic

molecules function as detergents (soaps) to
solubilize fats and oils.
When you wash your hands with soap, the greasy oil
molecules in the dirt on your hands partition into
the hydrophobic interior of soap micelles, and are
thereby solubilized and washed away.

Fat molecule

Fatty acid (detergent)

micelle
7
J G Burr, 9/1/14

Saturated vs. unsaturated fatty acids:

Some fatty acids are saturated (no C=C double bonds):

Others are unsaturated (have a C=C double bond), or

polyunsaturated (two or more C=C double bonds):

8
J G Burr, 9/1/14

Organic chemistry review: Cis vs. Trans

configuration about the C=C double bond
In biologically synthesized unsaturated fatty acids, the C=C double
bond is almost invariably in the cis configuration (the two methyl
groups are on the same side of the C=C double bond. This is
energetically unfavorable, since the methyl groups sterically hinder
each other (tend to bump into each other).

What we find
in cellular
lipids.

cis:

As we saw in the preceding slide, the

cis configuration introduces a kink
in the fatty acid hydrocarbon chain.

The thermodynamically more favored arrangement is for the methyl

groups to be in the trans configuration, where there is no steric
hindrance:
When the C=C methyl groups are in
trans:

the trans configuration, there is no

kink in the fatty acid hydrocarbon
chain.
9
J G Burr, 9/1/14

Fats in which the substituent fatty acids are largely

saturated are solid at room temperature (butter,
cheese). These are typically animal fats.
A fat
molecule with
three
saturated
fatty acids
attached to
the glycerol
backbone.
Notice the
close packing.
This is because the straight fatty acid chains in all the
individual molecules of fat can closely pack together to
form a kind of crystalline array.
10
J G Burr, 9/1/14

Whereas fats in which the substituent fatty acids are

largely unsaturated are liquid at room temperature
(Red atoms are carboxyl
(vegetable oils, fish oils).
A fat molecule
with three
unsaturated
fatty acids
attached to the
glycerol
backbone. Note
that the C=C
kinks will
prevent tight
packing of the
fat molecules.

oxygen participating in
the ester linkage to the
glycerol backbone.)

This is because the kinked fatty acid chains in all the fat
molecules are not easily able to pack closely together.

11
J G Burr, 9/1/14

Whereas fats in which the substituent fatty acids are

largely unsaturated are liquid at room temperature
(vegetable oils, fish oils).
(Red-orange atoms are
A fat molecule
with three
unsaturated
fatty acids
attached to the
glycerol
backbone. Note
that the C=C
kinks will
prevent tight
packing of the
fat molecules.

carboxyl oxygen
participating in the ester
linkage to the glycerol
backbone.)

This is because the kinked fatty acid chains in all the fat
molecules are not easily able to pack closely together.

12
J G Burr, 9/1/14

Sidebar on trans fatty acids:

Margarine is usually made by chemically hydrogenating the (kinked)

unsaturated fats in vegetable oil, to convert them to (straight)

saturated fats. This is done by treating the oil with a combination of
heat and pressurized hydrogen gas.
The hydrogen gas converts many of the -C=C- bonds to CH 2-CH2- bonds,
but not all of them; and the heat permits many of the remaining cis -C=Cbonds originally present in the oil to isomerize to the more stable trans
-C=C- configuration.
So partially hydrogenated vegetable oils, which are used not only in
margarine, but many other foods found in the supermarket, are rich in
trans fatty acids.
Since trans fatty acids are generally not found in nature, our bodies are
not able to metabolize them well, and they tend to inhibit important
enzymes involved in lipid metabolism. In recent years, for example, we
have learned that they contribute to a rise in bad LDL particles in the
blood and a decrease in good HDL particles. (HDL and LDL particles
are involved in cholesterol transport in the blood.)
13
J G Burr, 9/1/14

Sidebar on polyunsaturated fatty acids:

There are two polyunsaturated fatty acids that cannot be
synthesized by mammals, and must therefore be taken in by the
diet. These two essential fatty acids are linoleic acid and
alpha-linolenic acid:
Omega-6 because the nearest C=C is 6 carbon atoms away
from the carbon

An omega-6
fatty acid

Vegetable
oils (corn oil)

6
1
(Also known as an 18:2 delta 9,12 fatty acid,
numbering from the carboxyl carbon)

An omega-3
fatty acid

(ALA)
(Also known as an 18:3 delta 9,12,15 fatty
acid, numbering from the carboxyl carbon)

Certain other
vegetable oils
(eg, flaxseed)
and fish oils
(eg, salmon) are
rich in -3
fatty acids.
14
J G Burr, 9/1/14

Omega-3 and omega-6 fatty acids are used to

synthesize 20-carbon polyunsaturated fatty acids,
known as eicosinoids.
The -3 eicosinoid Eicosapentaenoic Acid (EPA)
(derived from -3 alpha linolenic acid) (ALA)

Certain fish oils are rich in -3 eicosapentaenoic acid

(EPA) (eg, salmon); these fish oils are also rich in ALA.

Eicosinoids are acted on by enzymes called

cyclooxygenases (COX) to produce signaling
molecules called prostaglandins.
15
J G Burr, 9/1/14

Certain prostaglandins are inflammatory, others inhibit

inflammation. The prostaglandins derived from omega-6
fatty acids tend (when in excess) to produce clotting
and inflammation; whereas those derived from omega-3
fatty acids have the opposite effect. Most modern
western diets are deficient in omega-3 fatty acids.
Eat more fish!
COX
enzyme

-3 Eicosapentaenoic Acid (EPA)

(derived from ALA)

Prostaglandin D3
(anti-inflammatory)

(Aside: Aspirin and related drugs (eg, ibuprofen) inhibit a cyclooxygenase (COX)
enzyme that plays a role in the synthesis of inflammatory prostaglandins from
the -6 linoleic acid-derived eicosinoid, arachidonic acid.)
16
J G Burr, 9/1/14

Now lets turn our attention to phospholipids.

But first:
Remember, in the case of fats, all three of the
hydroxyl groups on glycerol are esterified to fatty
acids:

In the case of phospholipids, only two of the three

hydroxyl groups are esterified to fatty acids; the
third one is esterified to phosphoric acid.

17

J G Burr, 9/1/14

Phospholipid structure:

Phosphoric acid is
esterified to one of the
3 hydroxyl groups of
glycerol

Another polar group (in this case,

serine) is also esterified to the
phosphoric acid moiety. (In other
cases the polar group is choline, or
ethanolamine, or inositol.)

Phosphoric acid

These are 4
different
representations
of the same thing:
a phospholipid
molecule.

Long-chain fatty acids

esterified to the
other 2 hydroxyl
groups of glycerol

glycerol

Four different depictions of the same

phospholipid molecule

18
J G Burr, 9/1/14

Aside: A previous edition of your text showed that in some phospholipids,

isoprene chains are bound via ether linkages to glycerol, instead of fatty
acid chains via an ester linkage. These isoprene-based phospholipids are
found only in the bacteria-like organisms that comprise the domain
Archaea.

Phospholipids based on fatty acids are by far the most predominant in

living organisms.

Phospholipids based
on poly-isoprene
chains.
(Found only in
Archaea.)

Phospholipids based
on fatty acids.
(Found in all other
organisms.)

19
J G Burr, 9/1/14

Like fatty acids, phospholipids are also

amphipathic molecules: hydrophilic at one
end, hydrophobic at the other:
Hydrophilic headgroup

Hydrophobic
hydrocarbon tails

Four different depictions of the same

phospholipid

20
J G Burr, 9/1/14

Phospholipids spontaneously form bilayers

Phospholipid bilayer

Aqueous
compartment
(eg, outside
cell)

Aqueous
compartment
(eg, inside cell

21
J G Burr, 9/1/14

Why is it that fatty acids (and detergents in

general) form spherical micelles, whereas
phospholipids form planar bilayers?
In part, it has to do with the shape and charge properties of the
two types of molecules. Fatty acids are effectively cone shaped,
whereas phospholipids are more tubular.

Detergent molecule

Phospholipid molecule

22
J G Burr, 9/1/14

Planar phospholipid bilayers are not

energetically favorable; they close to form
hollow (water filled) vesicles:

Phospholipid
vesicle

Your text explains that

artificially created
phospholipid vesicles are
called liposomes.
23
J G Burr, 9/1/14

The phospholipid bilayer is a two-dimensional

fluid -- phospholipid molecules can diffuse in the
plane of the membrane:
The lateral diffusion rate of a
phospholipid molecule is 2/sec

1 sec

bacterium

24
J G Burr, 9/1/14

Phospholipid bilayers can melt or freeze,

depending on the temperature.
Consider the two structures shown here for a theoretical lipid
membrane, consisting of phospholipids with saturated fatty acids:
Warm temperature

Fluid, vegetable oil-like

Cold temperature

Solid, butter-like

25
J G Burr, 9/1/14

The higher the percentage of phospholipids with

(cis) unsaturated fatty acids in the membrane,
the more fluid the membrane will be at any given
temperature:

The cis double bonds make it more difficult to pack the chains
together, thereby making the membrane more difficult to
freeze. In addition, because the fatty acids of unsaturated
lipids are more spread apart, the lipid bilayers containing them
are thinner, and more porous.

26
J G Burr, 9/1/14

Bacteria and cold-blooded organisms like fish can

adjust the ratio of saturated to unsaturated
phospholipids in their surface membrane when it
gets hot or cold outside. In this way they prevent
the membrane from freezing when it is too cold,
or getting too permeable when it is too hot.

27
J G Burr, 9/1/14

Now lets talk about the 3rd biologically important

lipid-- Cholesterol:

Four different depictions of a cholesterol molecule

28
J G Burr, 9/1/14

Cholesterol fills in the spaces in lipid bilayers

containing (cis) unsaturated fatty acids:

Animal cell membranes have a high percentage of lipids with

unsaturated fatty acids. Consequently, they are very fluid. In
the absence of cholesterol, they would be too fluid!
29
J G Burr, 9/1/14

Lipid bilayers with unsaturated fatty acids are

more permeable (too permeable), compared to
lipid bilayers with 100% saturated fatty acids
(which are too impermeable to small polar
molecules like glycerol or water)

30
J G Burr, 9/1/14

Adding cholesterol to lipid bilayers with

unsaturated fatty acids decreases the
permeability of the bilayer (to an appropriate
level of permeability)

Animal cell surface

membranes contain
approximately 20%
cholesterol

31
J G Burr, 9/1/14

In recent years, the Singer-Nicholson model has

been refined with the discovery that the lipid
bilayer contains cholesterol-rich patches of
particular lipids, called lipid rafts.
Well have more to say about this next year in
BIO 3302 (Molecular Cell Biology)

32
J G Burr, 9/1/14