Components of Biological Membranes

Introduction.
 
Biological membranes surround all living cells, and may
also be found surrounding many of an eukaryotes organelles.
The membrane is essential to the survival of a cell due to
its diverse range of functions. There are general functions
common to all membranes such as control of permeability,
and then there are specialised functions that depend upon
the cell type, such as conveyance of an action potential in
neurones. However, despite the diversity of function, the
structure of membranes is remarkably similar.
 
All membranes are composed of lipid, protein and
carbohydrate, but it is the ratio of these components that
varies. For example the protein component may be as high as
80% in Erythrocytes, and as low as 18% in myelinated
neurones. Alternately, the lipid component may be as high
as 80% in myelinated neurones, and as low as 15% in
skeletal muscle fibres.
 
The initial model for membrane structure was proposed by
Danielli and Davson in the late 1930s. They suggested that
the plasma membrane consisted of a lipid bilayer coated on
both sides by protein. In 1960, Michael Robertson proposed
the Unit Membrane Hypothesis which suggests that all
biological membranes -regardless of location- have a
similar basic structure. This has been confirmed by
research techniques. In the 1970s, Singer and Nicholson
announced a modified version of Danielli and Davsons
membrane model, which they called the Fluid Mosaic Model.
This suggested that the lipid bilayer supplies the backbone
of the membrane, and proteins associated with the membrane
are not fixed in regular positions. This model has yet to
be disproved and will therefore be the basis of this essay. 

The lipid component.
 
Lipid and protein are the two predominant components of the
biological membrane. There are a variety of lipids found in
membranes, the majority of which are phospholipids. The
phosphate head of a lipid molecule is hydrophilic, while
the long fatty acid tails are hydrophobic. This gives the
overall molecule an amphipathic nature. The fatty acid
tails of lipid molecules are attracted together by
hydrophobic forces and this causes the formation of a
bilayer that is exclusive of water. This bilayer is the
basis of all membrane structure. The significance of the
hydrophobic forces between fatty acids is that the membrane
is capable of spontaneous reforming should it become
damaged.
 
The major lipid of animal cells is phospatidylcholine. It
is a typical phospholipid with two fatty acid chains. One
of these chains is saturated, the other unsaturated. The
unsaturated chain is especially important because the kink
due to the double bond increases the distance between
neighbouring molecules, and this in turn increases the
fluidity of the membrane. Other important phospholipids
include phospatidylserine and phosphatidylethanolamine, the
latter of which is found in bacteria.
 
The phosphate group of phospholipids acts as a polar head,
but it is not always the only polar group that can be
present. Some plants contain sulphonolipids in their
membranes, and more commonly a carbohydrate may be present
to give a glycolipid. The main carbohydrate found in
glycolipids is galactose. Glycolipids tend to only be found
on the outer face of the plasma membrane where in animals
they constitute about 5% of all lipid present. The precise
functions of glycolipids is still unclear, but suggestions
include protecting the membrane in harsh conditions,
electrical insulation in neurones, and maintenance of ionic
concentration gradients through the charges on the sugar
units. However the most important role seems to be the
behaviour of glycolipids in cellular recognition, where the
charged sugar units interact with extracellular molecules.
An example of this is the interaction between a ganglioside
called GM1 and the Cholera toxin. The ganglioside triggers
a chain of events that leads to the characteristic
diarrhoea of Cholera sufferers. Cells lacking GM1 are not
affected by the Cholera toxin.
 
Eukaryotes also contain sterols in their membranes,
associated with lipids. In plants the main sterol present
is ergosterol, and in animals the main sterol is
cholesterol. There may be as many cholesterol molecules in
a membrane as there are phospholipid molecules. Cholesterol
orientates in such a way that it significantly affects the
fluidity of the membrane. In regions of high cholesterol
content, permeability is greatly restricted so that even
the smallest molecules can no longer cross the membrane.
This is advantageous in localised regions of membrane.
Cholesterol also acts as a very efficient cryoprotectant,
preventing the lipid bilayer from crystallising in cold
conditions.
 
The biological membrane is responsible for defining cell
and organelle boundaries. This is important in separating
matrices that may have very different compositions. Since
there are no covalent forces between lipids in a bilayer,
the individual molecules are able to diffuse laterally, and
occasionally across the membrane. This freedom of movement
aids the process of simple diffusion, which is the only way
that small molecules can cross the membrane without the aid
of proteins. The limit of permeability of the membrane to
the diffusion of small solutes is selectively controlled by
the distribution of cholesterol.
 
Another role of lipids is their to dissolve proteins and
enzymes that would otherwise be insoluble. When an enzyme
becomes partially embedded in the lipid bilayer it can more
readily undergo conformational changes, that increase its
activity, or specificity to its substrate. For example,
mitochondrial ATPase is a membranous enzyme that has a
greatly decreased Km and Vmax following delipidation. The
same applies to glucose-6-phospatase, and many other
enzymes.
 
The ability of the lipid bilayer to act as an organic
solvent is very important in the reception of the
Intracellular Receptor Superfamily. These are hormones such
as the steroids, thyroids and retinoids which are all small
enough to pass directly through the membrane.
 
Ionophores are another family of compounds often found
embedded in the plasma membrane. Although some are
proteinous, the majority are polyaromatic hydrocarbons, or
hydrocarbons with a net ring structure. Their presence in
the membrane produces channels that increases permeability
to specific inorganic ions. Ionophores may be either mobile
ion-carriers or channel formers. (see fig.4)
 
The two layers of lipid tend to have different functions or
at least uneven distribution of the work involved in a
function, and to this end the distribution of types of
lipid molecules is asymmetrical, usually in favour of the
outer face. In general internal membranes are also a lot
simpler in composition than the plasma membrane.
Mitochondria, the endoplasmic reticulum, and the nucleus do
not contain any glycolipids. The nuclear membrane is
distinct in the fact that over 60% of its lipid is
phospatidylcholine, whereas in the plasma membrane the
figure is nearer 35%. The protein component.
 
All biological membranes contain a certain amount of
protein. The mass ratio of protein to lipid may vary from
0.25:1 to 3.6:1, although the average is usually 1:1. The
proteins of a biological membrane can be classified into
five groups depending upon their location, as follows; 
Class 1. Peripheral.------------These proteins lack anchor
chains. They are usually found on the external face of
membranes associated by polar interactions. 
Class 2. Partially Anchored-----These proteins have a short
hydrophobic anchor chain that cannot completely span the
membrane. 
Class 3. Integral (1)-----------These proteins have one
anchor chain that spans the membrane. 
Class 4. Integral (5)-----------These proteins have five
anchor chains that span the membrane. 
Class 5. Lipid Anchored---------These proteins undergo
substitution with the carbohydrate groups of glycolipids,
therefore binding covalently with the lipid. 
This classification is not definitive in including all
proteins, since there may well be other examples that span
the membrane with different numbers of anchor chains.
 
The structure of proteins varies greatly. The first factor
affecting structure is the proteins function, but equally
important is the proteins location, as shown above. Those
proteins that span the membrane have regions of hydrophobic
amino acids arranged in alpha-helices that act as anchors.
The alpha-helix allows maximum Hydrogen bonding, and
therefore water exclusion.
 
Proteins that pass completely through the membrane are
never symmetrical in their structure. The outer face of the
plasma membrane at least always has the bulk of the
proteins structure. It is usually rich in disulphide bonds,
oligasaccharides, and when relevant, prosthetic groups.
 
The proteins found in biological membranes all have
distinctive functions, such that the overall function of a
cell or organelle may depend on the proteins present. Also,
different membranes within a cell, (i.e. those membranes
surrounding organelles) can be recognised solely on the
presence of membranous marker proteins.
 
In the majority of cases membranous proteins perform
regulatory functions. The first group of such proteins are
the ionophores, as mentioned before. The proteinous
ionophores are found in the greatest concentration in
neurones. Here, the diffusion of inorganic ions is
essential to maintaining the required membrane potential.
The main ions responsible for this are Sodium, Potassium
and Chloride - each of which has its own channel forming
ionophore.
 
The observed rate of diffusion of many other solutes is
much greater than can be explained by physical processes.
It is widely accepted that membranous proteins carry
certain solutes across the membrane by the process of
facilitated diffusion. This is done by the forming of pores
of a complimentary size and charge, to accept specific ions
or organic molecules. The pores are opened and closed by
conformational changes in the proteins structure. There are
three main types of facilitated diffusion. None of these
processes require an energy input.
 
Active transport is the movement of solutes across a
membrane, against the concentration gradient, and it
therefore utilises energy from ATP. An example of this is
the Sodium-Potassium-ATPase pump, which is an active
antiport carrier protein common to nearly all living cells.
It maintains a high [Potassium ion] within the cell while
simultaneously maintaining a high [Sodium ion] outside the
cell. The reason for this is that by pumping Sodium out of
the cell, it can diffuse in again at a different site where
it couples to a nutrient.
 
As well as transporting solutes across a membrane, there
are many proteins that transport solutes along the
membrane. An example of this are the respiratory enzyme
complexes of the inner mitochondrial membrane. These
complexes are located in a close proximity to each other,
and pass electrons through what is known as the respiratory
chain. The orientation of the complexes is vital for their
correct functioning.
 
Another key role of membranous proteins is to oversee
interactions with the extracellular matrix. Many hormones
interact with cells through the membranous enzyme -
adenylcyclase. The binding of specific hormones activates
adenylcyclase, to produce cyclic adenosine monophosphate
(c.AMP) from adenosine triphosphate (ATP). c.AMP acts as a
secondary messenger within the cell. A wide variety of
extracellular signalling molecules work by controlling
intracellular c.AMP levels. Insulin is an exception to this
generalisation, because its receptor is enzyme linked
rather than ligand linked. This means that the cystolic
face of the receptor has enzymatic activity rather than
ligand forming activity. The enzymatic activity of the
Insulin receptor is in the reversible phosphorylation of
phospoinosite.
 
Vision and smell rely on a family of receptors called the
G-protein receptors. The cystolic faces of these receptors
bind with guanosine triphosphate (GTP). This action is
coupled to ion channels, so that the activation of a
receptor changes the intracellular levels of c.GMP, which
in turn activates the ion channels, and thus allows a
membrane potential to be developed.
 
The composition of proteins in the biological membrane is
far from static. Receptors are constantly being regenerated
and replaced, and this is important in the ever changing
environment of the cell. For example, the transferrin
receptor is responsible for the uptake of Iron. In the
cytosol, an enzyme called aconitase is present which
inhibits the synthesis of transferrin by binding to
transferrins mRNA. In a low Iron concentration, aconitase
releases the mRNA allowing transferrin to be synthesised.
 
A similar process occurs with the Low Density Lipoprotein
(LDL) receptor. This receptor traps LDL particles which are
rich in cholesterol. The LDL receptor is only produced by
the cell, when the cell requires cholesterol for membrane
synthesis.
 
The number of receptors in a biological membrane varies
greatly between different type of receptor.
 
The immune responses of cells are controlled by a
superfamily of membranous proteins called the Ig
superfamily. This superfamily contains all the molecules
involved in intercellular and antigenic recognition. This
includes major histocompatability complexes, Thymus
T-cells, Bursa B-cells, antibodies and so on. Although this
family is vast, the important point is that all antigenic
responses are mediated by membranous proteins.
 
As there are glycolipids in the biological membrane, there
are also glycoproteins. One of the key roles of
glycoproteins is in intercellular adhesion. The Cadherins
are a family of Calcium dependant adhesives. They are
firmly anchored through the membrane, and have glycolated
heads that covalently bind to neighbouring molecules. They
seem to be important in embryonic morphogenesis during the
differentiation of tissue types. The Lectins and Selectins
are similar families of molecules responsible for adhesion
in the bloodstream. However the most abundant adhesives are
the Integrins, which are responsible for binding the
cellular cytoskeleton to the extracellular matrix.
 
The range of membranous proteins has proved to be vast, due
to the wide variety of functions that must be performed. It
would be possible to continue describing proteins for many
more pages, but one final example will be used in
conclusion, and that is the photochemical reaction centre
of photosynthesis. This very large protein complex is found
in the Thylakoid membrane of chloroplasts. Each reaction
centre has an antenna complex comprising hundreds of
chlorophyll molecules that trap light and funnel the energy
through to a trap where an excited electron is passed down
a chain of several membranous electron acceptors.
Conclusion.
 
The role of the biological membrane has proved to be vital
in countless mechanisms necessary to a cells survival. The
phospholipid bilayer performs the simpler functions such as
compartmentation, protection and osmoregulation. The
proteins perform a wider range of functions such as
extracellular interactions and metabolic processes. The
carbohydrates are found in conjunction with both the lipids
and proteins, and therefore enhance the properties of both.
This may vary from recognition to protection.
 
Overall the biological membrane is an extensive,
self-sealing, fluid, asymmetric, selectively permeable,
compartmental barrier essential for a cell or organelles
correct functioning, and thus its survival.
 
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