Plasma membrane is about 50 atoms thick and serves as a

selective barrior.

Membranes include 1. sensors which enable the cell to respond to the

environment and 2. highly selective channels and pumps. Mechanical

properties of the membranes are remarkable. Enlarges and changes

shape as needed with no loss of integrety.

Eucaryotic cells

contain many

compartments created

by intracellular

membranes

The lipid bilayer.

A. An electron micrograph

The lipids in the cell

membrane are

amphipathic.

Phosphatidylcholine is the most common type of phospholipid.

Positive

negative

Three kinds of membrane lipids, all amphipathic, incude phospholipids,

sterols, and glycolipids.

Hydrophilic heads

Hydrophilic molecules interacting with

water molecules.

Hydrophobic molecules in water. Water molecules

form a more ordered structure. See question 1.

Purely

hydrophobic

molecules

coalesce into

a single drop

in water.

Amphipathic molecules

like

phosphotidylethanolamine

form a lipid bilayer -

energetically most

favorable.

Self-sealing property

“free edges” are quickly

eliminated because they are

energetically unfavorable -

hydrophobic areas are in

contact with water.

The lipids will spontaneously

seal and will always form a

closed compartment.

A small tear will be repaired. A

larger tear may lead to the

break up of the membrane into

separate vesicles.

With water inside and out, the lipid bilayer remains intact, no

lipids leave. However, the lipids do move freely within the

bilayer. Experiments use liposomes, which form spontaneously.

Or flat bilayers formed across a hole in a partition between to aqueous

compartments. The fluidity of the lipid bilayer is crucial for the

function of the membrane. In these experimental systems

phospholipids very rarely flip from one layer to the other without

proteins to facilitate the process.

Due to thermal motions, lipid molecules within a monolayer rotate very

rapidly and diffuse rapidly through the fluid membrane. Any drop in

temperature decreases the rate of lipid movement, making the lipid

bilayer less fluid. This inhibits many functions of the cell’s membranes.

All this has been

confirmed in whole

cells.

• The fluidity of a lipid bilayer depends on its

composition.

– As temperature and environment changes, the

fluidity of the cell’s membranes must be kept

functional.

– The closer and more regular the packing of the

tails, the more viscous and less fluid the bilayer

will be

– The length and degree of saturation with

hydrogens affect their packing

• shorter tails can not interact as much - more fluid

• one of the two hydrocarbon tails often has a double

bond - unsaturated. This creates a kink - less

packing, more fluid.

Plant fats are generally unsaturated and liquid at room temperature.

Animal fats are solid at room temperature. Hydrogenated plant fats are

no longer unsaturated.

• In bacterial and yeast cells, both the lengths

and the unsaturation is constantly adjusted

to maintain the membrane at a relatively

constant fluidity.

– At higher temperatures the cell makes longer

tailed lipids with fewer double bonds.

• In animal cells, membrane fluidity is

modulated by cholesterol, which is absent in

plants, yeast and bacteria.

Cholesterol fills in the spaces left by the kinks; stiffens the bilayer and

makes it less fluid and less permeable.

• Membrane fluidity is important to a cell for many

reasons.

– 1. Enables membrane proteins to diffuse rapidly and

interact with one another - crucial in cell signaling etc.

– 2. Provides a simple means of distributing membrane

lipids and proteins by diffusion from sites of insertion.

– 3. Allows membranes to fuse with one another and mix

their molecules

– 4. Ensures that membrane molecules are distributed

evenly between daughter cells.

• Remember though, cell has control - cytoskeleton

and other interactions can limit the mobility of

specific lipids and proteins.

The lipid bilayer is asymmetrical, with the cytoplasmic side being

different from the non-cytoplasmic side. Proteins are embedded with a

specific orientation crucial for their function. Phospholipid composition

also varies.

New phospholipid molecules are synthesized in the ER by membrane-

bound enzymes which use substrates (fatty acids) available only on one

side of the bilayer.

Flipases transfer specific phospholipid molecules selectively so that

different types become concentrated in the two halves. One sided

insertion and selective flippases create an asymmetrical membrane

In eucaryotic cells nearly all new membrane synthesis occurs in the ER.

The new membrane is exported to the golgi apparatus for modification

and export. Carbohydrate chains are added in the golgi - glycolipids.

The enzymes that add sugar groups to lipids are confined to the golgi

apparatus and sugars are added only to the non-cytoplasmic side. No

flippases exist for glycolipids. Forms a protective coat on most animal

cells.

Intracellular signal transduction

Lipids are made in the ER and transported via vesicles to their

destination. This form of transport preserves the cytoplasmic face and

the non-cytoplasmic face which is exposed to the exterior of the cell or

the interior of an organelle.

Lipid bilayers are impermeable

to solutes and ions. Rate of

diffusion varies depending on

size and solubility properties.

This has been demonstrated in

synthetic bilayers.

In this way,

cells control the

passage of

molecules

across its

membranes

Specialized transport proteins

transfer specific substrates

across the membrane

A crucial function of any cell membrane is to act as a barrior and to

control the passage of molecules across it.

The proteins in membranes serve many functions besides transporting nutrients etc.

Linkers link intracellular actin filaments to extracellular matrix proteins. Receptors

bind hormones and other signaling molecules and transmit that signal to the interior of

the cell. Enzymes catalyze specific reactions - example: flippases.

Membrane proteins associate with the lipid bilayer in three main ways.

All membrane proteins have a unique orientation - a particular section

always facing the cytosol. This is a consequence of how they are made.

Integral membrane proteins (transmembrane and lipid-linked) can be

isolated from the lipid membrane only by harsh treatment (detergent)

whereas peripheral membrane proteins can be released by relatively

gentle extraction methods.

1. 2. 3.

Membrane proteins have a unique orientation. Always has the

same region of the protein facing the cytosol. This depends on

how it was made.

Transmembrane proteins usually cross the bilayer as alpha-

helices. Sometimes as beta-barrels

Transmembrane portions are composed largely of amino acids with

hydrophobic side chains. However, the peptide back bone (peptide

bonds) is hydrophilic. Therefore, a helical structure is the most

energetically favorable.

The peptide bonds are

hydrogen bonded to each

other in the interior while the

hydrophobic amino acid side

chains contact the lipid

chains.

Many transmembrane proteins cross the membrane only once. Many

receptors for extracellular signals include an extracellular portion which

binds the signal molecule (hormone etc.). Binding of the signal molecule

induces a change in shape in the cytoplasmic part, which then signals to

the cell’s interior.

Other transmembrane proteins form aqueous pores that allow water-

soluble molecules to cross the membrane. These are more complicated,

often cross the bilayer a number of times as alpha-helices or as beta-

barrels

In these cases alph-

helices contain both

hydrophobic and

hydrophilic amino acid

side chains, with the

hydrophobic side chains

on one side and

hydrophilic on the other

side.

Although the alpha-helix is the most common, transmembrane portions

of a protein can be beta-barrels (two beta-sheets connected by a disulfide

bond. The loop areas often form the active site or binding site.

Beta-barrels

are less

versatile since

the can form

only wide

channels.

To study proteins,

they can be isolated

from the lipid bilayer

by solubilization

using detergents.

Detergents are small,

amphipathic, lipidlike

molecules with only a

single hydrophobic

tail. The protein-

detergent complexes

can then be separated

by SDS

polyacrylamide gel

elctrophoresis

(Chapter 5).

The complete structure of membrane proteins is difficult. They do not

crystallize well for X-ray crysallography (Chapter 5). This is

bacteriorhodopsin.

A small protein

which acts as a

membrane

transport protein

that pumps H+ out

of the bacterium.

It gets its energy

from light, which

is absorbed by

retinal.Retinal

changes shape

The structure of a

bacterial

photosynthetic

reaction center

includes four

protein

molecules.

The plasma membrane must be strengthened by the cell cortex. This is a

framework of proteins attached to the membrane via transmembrane

proteins.The shape and mechanical properties of the plasma membrane is

determined by a meshwork of fibrous proteins - the cell cortex.

Red blood cells

are very simple,

allowing study

of the cell

cortex in simple

form.

Genetic

abnormalities in

spectrin structure

result in anemia,

spherical, fragile

rbcs

The spectrin-based cell cortex of human red blood cells. Much simpler

than other cells.

Dystrophin in muscular

dystrophy

Most of the proteins in the plasma membrane have short chains of sugars

(oligosaccharides) linked to them - glycoproteins. Others have longer

polysaccharide chains - proteoglycans. All the glycoproteins,

proteoglycans, and glycolipids are found on the noncytosolic side of the

lipid membrane. They form a sugar coating called the glycocalyx.

Glycocalyx halps

to protect the cell

surface from

mechanical and

chemical damage,

absorb water and

give the cell a

slimy surface to

help cells squeeze

through narrow

spaces and prevent

them from sticking

to each other or the

walls of blood

vessels.

Besides protection and lubrication, the glycocalyx is important in cell-

cell recognition and adhesion. Some proteins (lectins) recognize

particular oligosaccharide side chains and bind to them. The short

oligosaccharides are enormously diverse, joined in different ways,

branched, very complex and hard to study. Ex. Recognition of an egg

by a spermSpecific carbohydrate

chains on the surface of

neutrophils binds a lectin

on the cells of the blood

vessels at the site of

infection. Allowing them

to stick transiently and

then bind more strongly to

other adhesion molecules.

In this way the phagocytes

enter and ingest the

bacteria.

The lipid bilayer is a two-dimensional fluid. Many lipids and proteins

move freely within the plane. This is demonstrated by staining mouse

cells with rhodamine and human cells with fluorescein. These two cells

are then fused. Within 30 minutes the proteins from the mouse and

human cells have diffused and are intermixed.

However, lipids and proteins do not all float freely in the membrane.

The cell controls the movement of many proteins. Cells have ways of

confining particular plasma membrane proteins to localized areas,

creating membrane domains which are functionally specialized.

Proteins are

moved together

when signaled by

receptors like

adhesion

molecules.

Tethered to the

cell cortex

Bound by the

extracellular matrix

Held by proteins on another cell

Stopped by

diffusion

barriors.

In epithelial cells that line the gut, uptake of nutrients from the gut is

confined to the apical surface while proteins involved in the transport of

solutes out into the tissues and bloodstream is confined to the basal and

lateral surfaces. This asymmetric distribution is maintained by abarrier

formed by tight junctions - seals between adjacent cells.