Essay/Term paper: What are the major components of biological membranes and how do they contribute to membrane function?.

Essay, term paper, research paper:  Biology

What Are The Major Components of Biological Membranes And How Do They Contribute
To Membrane Function?.


Summary.

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.

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.

Bibliography.

1) Alberts,B; Bray,D; Lewis,J; Raff,M; Roberts,K; Watson,J.D. Molecular
Biology of the Cell, Third Edition. p.195-212, p.478-504. Garland
Publishing,
1994. 2) Beach; Cerejidol; Gordon; Rotunno. Introduction to the
study of Biological
Membranes. p.12. 1970. 3) Fleischer; Haleti; Maclennan; Tzagoloff.
The Molecular Biology of
Membranes. p.138-182. Plenum Press, 1978. 4) Perkins,H.R;
Rogers,H.J. Cell Walls and Membranes. p.334-338. E & F.N.
Spon Ltd, 1968. 5) Quinn,P. The Molecular Biology of Cell Membranes.
p.30-34, p.173-207.
Macmillan Press, 1982. 6) Stryer,L. Biochemistry, Third Edition.
p.283-309. W.H. Freeman & Co, 1994. 7) Yeagle,P. The Membranes of Cells.
p.4-16, p.23-39. Academic Press Inc,
1987.