Date sent:        Tue, 30 Apr 1996 12:23:52 +0100

Name:       essay.txt
Uploader:   Stuart Wigley
Email:      lsuqz@csv.warwick.ac.uk
Language:   English
Subject:    Biology
Title:      What are the major components of biological membranes and how do they contribute
to membrane function? Grade:      ~80% System:     University Age:        18 (when handed
in) Country:    Britain Comments:   Overview of the structure and function of biological
membranes with specific examples Where I...: News groups



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.

