Membrane Structure

Lipids are insoluble because they are predominately

nonpolar, but they also contain polar groups (hydrophilic
head with hydrophobic tails)
o They are amphipathic, meaning they are hydrophobic
and hydrophilic
o They have one polar head group with two
hydrophobic hydrocarbon tails, usually fatty acids
o When a critical concentration (CMC) of lipids are
present in aqueous medium, they form micelles
(single layer of lipids with hydrophobic interior)
These can transport lipids in our blood
because they have a nonpolar interior
o A liposome may form when you sonicate an
amphipathic lipid in an aqueous medium (double layered lipid membrane) and is the
beginning of a cell
Due to the amphipathic nature of phospholipids
o Bilayers form spontaneously (no energy required)
o The cell is a vesicle
o The head group is more electron dense that the fatty acids and results in a trilaminar
appearance
o Phospholipid bilayers are impermeant to hydrophilic substances
The basic components of the plasma membrane are proteins (30%), phospholipids (30%), and
sterols (19%)
o Membrane composition is dictated by organism, tissue, cell function, and temperature

Choline phospholipid: phosphate has a charge which

makes it hydrophobic
o The cis double bond affects how they pack
together
o One tail usually has one or more cis-double
bonds (unsaturated) while the other does not
(saturated)
The ratio of the amounts of each of
these two types of tails affects the
degree of packing of the
phospholipids
o Melting points are strongly influenced by the
fatty acid length and the degree of unsaturation
(fully saturated lipids can pack very close
together)
Simplest lipids are triacylglycerols (aka triglycerides,
fats) which are composed of three fatty acids in an ester
linkage to one glycerol
1,2,3-triacylglyerol 1,2-diacyl-snglycerol-3-phosphate

They are nonpolar, hydrophobic molecules

Glycerol is prochiral (meaning it can be converted into a chiral center (carbon atom with four
unidentical substituents) by changing only one of its attached groups)
Nomenclature
o Saturated fatty acids (-anoic)
o Monounsaturated fatty acids
(-enoic)
o Polyunsaturated fatty acids
o The saturation (or ) is
counted from the carboxyl
carbon COOH, while the
o n where n is the lower numbered carbon of the
double bond
o Ex: 20:4 5,8,11,14 where 20 = total number of
carbons, 4 = double bonds
o Also can be written as n where n is the number of
carbons from the methyl end until the first double
bond
o Last carbon is , then there are , , carbons right
next to the carboxyl carbon
There can be various head group substituents
o The simplest of which have a hydrogen (-1 charge)
o The most frequent head group is ethanolamine
o If the phosphates are at opposite positions then they
can be phosphorylated
o If the cells cannot be phosphorylated then they
become cancerous
Not all phospholipids come from fatty acids, they can also
have alcohol
o Ex: choline as head and acetyl ester in the 2 position
We can also have a double bond, as seen
in the linked alkene
Sphingolipids: Ceramide is the parent
compound for this group usually
o General structure of a sphingolipid
is an amide linkage at C2
o They are the sites of biological
recognition
o Sphingomyelins: contain phosphocholine or
phosphoethanolamine as their polar head group
Present in the plasma membranes of animal cells and are prominent in myelin
Are similar to glycerophospholipids: similar in their general properties/3D structure
and have neutral charge on head group
o Glycosphinogolipids: head groups with one or more
sugars connected directly to the OH at the C1 of
the ceramide, they do not contain phosphate
Cerebrosides: single sugar linked to
ceramide
Globosides: neutral with two or more sugars
They are determinants of blood group
o Gangliosides: most complex, contain
oligosaccharides as polar head group
Present on the outer membrane of cells for
recognition of intracellular molecules or
neighboring cells
o
o

Many are present in plasma membranes of neurons and are recognition sites: ex they help to
determine blood type

Sterols: structural lipids present in membranes of eukaryotic cells

o Has steroid nucleus with four fused rings, three with 6
carbons and one with 5
o Cholesterol: major sterol in animal tissues, is amphipathic
with polar head group and nonpolar hydrocarbon body
o Bacteria cannot synthesize sterols
o Sterols serve as precursors for variety of products with
specific biological activities: steroid hormones, acids etc
o They exist in the membrane and help to stabilize it, makes
fluid membranes more solid at different temperatures
Plasma membrane: defines
topological domains of the cell,
contains cellular components, and
excludes toxic materials
o You can solubilize membrane
proteins with a mild detergent,
which interrupts the lipid
bilayer and brings proteins
into solution as protein-lipiddetergent complexes.
Phospholipids in
membrane are also solubilized by detergents
Can use mild detergents for solubilizing, purifying,
and reconstituting functional membrane proteins.
Ex: Na+-K+ ATPase molecules are purified and
incorporated into phospholipid vesicles. The Na+-K+
ATPase is an ion pump
Fluidity
o The Tm is the transition temperature from the solid state to the fluid state: our membranes
must be in a fluid state
o The fluidity is determined in large part by the presence of double
bonds
o The short chains do not have as many links
to interact
o Doubles bonds lower the melting
temperature
o The physiological form is the cis: more
common and allows for packing efficiency
where the trans form is more elongated (do
not see as much in biological systems)
o Physical form at room temperature (C < 8 is
lipid, C > 10 is solid)
o Unsaturated fatty acids occupy more space
and resist packing
o Adding a single double bond creates a big
difference in the fluidity and melting point of
the fatty acid
o Cholesterol affects membrane fluidity by
stiffening a region

Mobility:
o Proteins: experiment done by mixing
plasma membranes of mouse and human
hybrid cells.
Proteins are initially confined to
their own halves of the newly
formed hybrid but they intermix
with time
Two antibodies used to visualize
the proteins are distinguished
using fluorescence microscopy
This proved that proteins can
move in a membrane
o Lipids: experiment done to measure
lateral diffusion rates of lipids by
fluorescence recovery after
photobleaching
Lipids in outer plasma membrane
are labeled with fluorescent probe
Small area is bleached by radiation
Over time, labeled lipids move into the bleached region
Rates of diffusion are typically high in lipid membranes
Cell membrane
o Spectrin based cytoskeleton of human red blood cell membrane
Spectrin dimers associate head to
head to form tetramers that are linked
in a netlike meshwork by junctional
complexes composed of short actin
filaments, tropomyosin, and adducing
Cytoskeleton is linked to the
membrane by indirect binding of
spectrin tetramers to some band 3
proteins via ankyrin molecules and
glycophorin
Allows some proteins to move
while others cant (those on band
3 and ankyrin)
This is mosaicism which gives
more structure to the cell
Rafts: enriched in sphlingolipids and cholesterol
o Responds to stress, antibody adhesion,
etc to bring things into or out of the cell
o Lots of cholesterol and doubly acylated
proteins
o Fatty acids can be in place on
proteins as post translational
modification
o Prenylated proteins are excluded
from the raft

o
o
o

Can be used to target regions in the cell

Docosahexaenoic acid also plays a role in rafts: has an aversion for cholesterol in
membranes 22:6 nomenclature
Usually associated with GPI anchored proteins

Caveolin is an integral membrane protein with two

globular domains connected by hair-pin shaped
hydrophobic domain which binds the protein to the
cytoplasmic leaflet of the plasma membrane
o Binds cholesterol to the membrane and forces
bilayer to curve inwards
o Involved in membrane trafficking and
transduction of extermal signals into cellular
responses
o Ex: insulin receptors and GTP-binding proteins
o Hyaluronic acid (HA) plays a large role in cell
migration
Ghosts: red blood cells tend to rupture in only one
place, giving rise to ghosts with only a single hole in them
o Smaller vesicles are produced by mechanically disrupting the ghosts, the orientation in
these vesicles can either be right-side-out or
inside-out, depending on the ionic conditions
during the disruption process
o Resealing with magnesium causes right-side-out
o Resealing without magnesium causes inside-out
o This allows you to see which proteins are inside
and which are outside
Asymmetric distribution of phospholipids between the
outer and inner monolayers of the erythrocyte plasma
membrane
o Determined by treating intact cell with
phospholipase C, which cannot reach lipids in
the inner monolayer (leaflet) but removes the
head groups of lipids in the outer monolayer.
o The proportion of each head group released
provides an estimate of the fraction of each lipid
in the outer monolayer

Lateral diffusion of lipids: they are free to move

laterally
o This happens very quickly
Transverse diffusion is catalyzed by flippases
o Mice that dont have this enzyme have
severe neurological problems as
uncatalyzed flipping takes days
Non catalyzed transverse diffusion
o Very energetically unfavorable

the

Lysophospholipids are missing a fatty acid tail and organize in a micelle

The more cylindrical form bilayers (all tend to have bulky head groups and bulky methyl groups)
Cone shaped: small hydrophilic and relatively big hydrophobic regions
Calcium promotes membrane to shift

THE CELL

Gut
o

Apical surface exposed to the tract and the

basolateral surface
o Nucleus has a double membrane (lipid bilayer)
o The nucleus membrane is continuous with the
endoplasmic reticulum
o It is bound to the endoplasm and has a double
membrane
The endoplasmic reticulum
o Contains more than half of the total cellular
membrane
o Highly convoluted but a single continuous sheet
o Encloses 10% of total cell volume
o Separated from the golgi system by two
membranes, from the cytosol and nucleus by
only one membrane
o Mediated transport from the cis to trans golig
o Does translational modification and sorting

Pulse Chase experiment: cells are supplied with precursor molecule in radioactive form
o Radioactive molecules mix with preexisting
unlabeled ones
o Changes in the location or chemical form of the
radioactive molecule can be followed as a function
of time
o The radioactive material is added and washed
away (pulse) and replaced by nonradioactive
molecules (chase)
o Chambers labeled A, B, C, D, represent different
compartments in the cell (detected by autoradiography or cell-fraction experiments) or
different chemical compounds (detected by chromatography or other chemical methods)
Golgi apparatus
o Traffic control point
o Convergence of biosynthesis, endocytosis,
recycling
o A series of subcompartments which serve as
separate environments

Procedure for the extraction, separation, and identification of cellular

lipids
o Tissue is homogenized in a chloroform/methanol/water mixture,
which on addition of the water and removal of the unextractable
sediment by centrifugation yields two phases
o Different types of extracted lipids in the chloroform phase may
be separated by adsorption chromatography on a column of
silica gel, through which solvents of increasing polarity are
passed
o They also may be separated by thin layer chromatography in
which lipids are carried up a silica gel collated plate by a rising
solvent front, less polar lipids traveling farther than more polar
or charged lipids
o TLC with appropriate solvents can also be used to separate
closely related lipid species
o The lipid fraction containing ester linked fatty acids is
transesterified in a warm aqueous solution of NaOH and
methanol, producing a mixture of fatty acyl methyl esters
o These methyl esters are then separated on the basis of chain
length and degree of saturation either by
Gas liquid chromatography
High performance lipid chromatography
o Determination of molecular mass by mass spectrometry allows
identification of individual lipids