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BIOPHYSICAL CHEMISTRY ESSAY: CELL MEMBRANE STRUCTURE AND PURPOSE
Cell membrane is a biological barrier that separates the interior part of the cell (i.e. the Cytoplasm, nuclei and the other cell organelle) from the outer environment, thus permits cellular individuality and also gives shape to the cell. This membrane is a mixture of lipids, protein and carbohydrates, therefore is a complex structure. The membrane is semi-permeable and thus only allows selective ions and molecules to go through it into the cell or leave the cell. This is achieved by formation of concentration gradient across the membrane, which many biological processes depend upon. The movement of the biological molecules across the membrane is either passive, which happens without the input of cellular energy or active transport that requires the cell to use energy. The cell membrane also helps in maintaining cell potential.
Proteins of the cell membrane form the essential component of the biological membrane since they function as pores, channels or transporters. Proteins thus have the capability of selective passage across the lipid bilayer. Some proteins that are embedded in the cell membrane act as molecular signals and therefore carry out communication. They act as receptors and receive signals from other cells or from the external environment and elicit a response in the cell. Some proteins function as markers which aid in identification of unknown cells. The membrane also aids in intercellular interactions.
The lipid bilayer of the cell membrane is only a few nanometres thick and is not permeable to most molecules that are soluble in water, and hence acts as a barrier to regulate the transport of ions, proteins and other molecules through the membrane. Since the phospholipid bilayer is not permeable to many ions, it helps in the regulation of salt concentration and pH by regulating the pumping of ions in and out of the cell via proteins called ion channel pumps.
The Fluid mosaic model is the most widely accepted biological membrane model that was proposed in the year 1972 by Singer and Nicolson. Floating in the phospholipid bilayer are molecules of protein, which is analogous to icebergs floating in a sea. The model is referred to as fluid because of the lateral motion of the bilayer macromolecules, and is referred to as mosaic because of the different molecular components .
Purpose of cell membrane
Cell membrane performs the following functions:
Membrane Transport of Small Molecules:
Transport proteins present in the bilayer can transport polar molecules through the membrane. There are various types of membrane transport proteins:
Uniport - This simply moves the solute from one side to the other side of the membrane.
Cotransport - This system moves two solutes simultaneously across the lipid bilayer. They are two types of this transport-symport (solutes are sent in the same direction) and antiport (solutes are passed in opposite directions).
These transports are come under the category of passive transport where no energy expenditure is involved. Here the solute moves from a higher concentration to a lower concentration gradient.
Examples of this include channel proteins, which allow the solute to pass if they are of a specific charge or size. Carrier proteins bind to the solute and help in its movement through the bilayer.
There are two main categories of transport of molecules are there in cells:
Small molecules like oxygen, ethanol and carbon dioxide pass through the membrane by simple diffusion (passive transport) down a concentration gradient. Transport of macromolecules like proteins, polynucleotides and polysaccharides is done by active transport using ATP, against the concentration gradient.
There are two types of active transport :
1) Exocytosis - Process by which waste substances are removed from the cell by vesicle formation and expulsion .
Figure 2: Exocytosis
2)Endocytosis-Â The molecule causes the cell membrane to bulge inward, thus forming a vesicle. Phagocytosis is a type of endocytosis where the whole cell is engulfed. Pinocytosis is another type when the external fluid is engulfed. Receptor-mediated endocytosis occurs when the material to be transported binds to specific molecules in the membrane. Example: transport of insulin and cholesterol into animal cells .
Figure 3: Endocytosis
Cell signalling across the membrane
Transmembrane signalling occurs through the generation of a number of signals like cyclic nucleotides, calcium, phosphoinositides and diacylglycerol. Specific signals of neurotransmitters hormones and immunoglobulins bind to the specific receptors on the membrane, which are mostly integral membrane proteins.
Figure 4: Signal transduction through membrane
This is the Ca2+-phosphatidylinositol signalling pathway which plays a major role in transmembrane signalling in a large number of different cell types.
This pathway leads to the activation of G-proteins. This initiates activation of phospholipase C and the subsequent formation of DAG and IP3Â which triggers the generation of repetitive [Ca2+]Â spikes .
Gap junctions are structures that allow the small molecules that are up to ~ 1200 Da to be transported from one cell's cytoplasm to the other. These structures contain proteins called connexins. Six connexins form a hemiconnexin and two hemiconnexins form a connexon. These connexions in the gap junction form cylindrical bridges through which substances are transported between cells .
Figure 5: Gap junction
The Fluid mosaic Model:
This model is the widely accepted membrane model. The membrane has a biomolecular lipid bilayer layer. There are proteins that are inserted in it or bound to the surface. Integral membrane protein is the proteins that are embedded in the membrane they play a key role as transporters for various molecules that cannot enter through the cell membrane. The integral proteins have an extra-cellular domain and cytoplasmic domain and are separated by a non-polar region that holds it tightly in the membrane. Proteins that are loosely bound to the to the outer membrane are called the peripheral proteins. Many of the proteins that are present and almost all the glycolipids have an externally oligosaccharides chains that are exposed outside the membrane .
Fig. 6: Fluid Mosaic Model
The membrane fluidity very much depends on the lipids concentration in the membrane. The hydrophobic chains of the fatty acids are much aligned therefore giving it a stiff structure. The transition(Tm) is the temperature at which the transition takes place from ordered to disordered state, this is the change that happens in the hydrophobic side chain. Cholesterol affects the fluidity of the membrane. It increases fluidity below Tm and decreases fluidity above Tm.
Modifications to the fluid mosaic model state that the lipids and proteins in the membrane are not randomly distributed. Randomness occurs when interaction energy of these molecules are close to their thermal energies. Since interaction energies cannot be in a narrow range due to large number of interactions, there is very less chance for randomness to occur. Hence the model was found to be "more mosaic than fluid" . The modified view of membrane model is shown in figure 7.
Figure 7: Modified view of cell membrane model 
Specialised structures in the membrane:
There are some special features in the membrane like lipid rafts, caveolae, tight junction, desmososmes, adherens junctions and microvilli. These are found in the recent years of research.
Lipids Raft is the area in the membrane that has relatively higher concentration of cholesterol, sphingo-lipids and some proteins, than the other parts of the membrane. It plays a major role in cell signal transduction. This is under research that if we increase the amount of this and clustering them closely may increase the overall efficiency of the cell.
Caveolae are special types of lipid rafts. Many of them have protein called caveolin-1 that is involved in the process. They were observed under electron microscope and were found to be flask-shaped. Proteins that are detected in this also play a role in signal transduction, example is insulin. Proteins found in this also play in role in folate receptor. This field is a growing interest for research.
Tight Junctions are present on the surface of the membrane and their major function is to prevent diffusion of macromolecules between cells. They are present below the apical surface of the epithelial cells. They are made up of various proteins including occludin, various claudins and junctional adhesion molecules .
DesmosomesÂ also called macula adherens are the specialised cell structures for cell to cell adhesion. Their function is to resist shearing force. They are mostly found in simpleÂ andÂ stratified squamous epithelium .
Adherens junctions are the proteins that usually occur at cell- cell junction .They are made up of proteins like cadherins, Î²-catenin, Î±-catenin and sometimes delta catenin. Their function is to provide strong adhesion between adjacent cells. They hold the cardiac muscleÂ cells firmly together as the heart beats and do not allow it to collapse .
Microvilli are very small finger like structures found on the cell membrane. They are mainly found on the epithelial cells, they increase the surface area of the cells therefore increasing the absorptive capacity of the cells. Actin filament extends from the end of these microvilli .
Components of cell membrane
Cell membrane is a complex structure and is composed of proteins, carbohydrates and lipids. Different cell membranes have different compositions.
Figure 8: Components of cell membrane
Phospholipids: There are two major class of phospholipids out of which in the cell membrane the phosphoglycerides are the most commonly found ones. Â Phospholglycerides are esters that are made up ofÂ two fatty acids, phosphoric acid and a trifunctional alcohol.
Phosphoglycerides with sphingomyelin have Sphingosine backbone instead of glycerol. They play a role in signal transduction. They are prominent in myelin sheaths .
Figure 9: Structure of phospholipid
Glycosphingolipids: These are sugar containing lipids that are present in the membrane. They have a backbone made of ceramides. These are amphipathic molecules consisting of a ceramide lipid anchor linked to an oligosaccharide chain of variable length and composition . They are required for proper functioning of nervous system. Determining their function will help to understand neurodegenerative disorders, cancer, immune function and diseases of metabolism .
Figure 10: Structure of glycosphingolipid
The most import sterol in the membrane is cholesterol.
Figure 11: Structure of cholesterol
Proteins in cell membrane
Integral membrane proteins: also calledÂ intrinsic proteins t has its some part of the protein embedded in the phospholipid bilayer. Most of these proteins have hydrophobic side chains that interact with membrane phospholipids fatty acyl groups. They are called transmembrane proteins if they one or more membrane spanning domains. The transmembrane proteins of the membrane spanning domains are made up of Î± helices or multiple Î² strands . These proteins are made up of two hydrophilic and one hydrobhobic region. The hydrophobic region traverses through the bilayer. They are asymmetric in nature. The transmembrane region of manyÂ integral membrane proteinsÂ is made up of a bundle of hydrophobic Î±-helices . Their major role is as transporters,Â and are also structural membrane-anchoring domains. They function by transporting hydrophilic molecules through the membrane. Many Integral Proteins Contain Multiple Transmembrane Î± lpha Helices .
Examples: Insulin receptor, Glycophorin, Rhodopsin, CD36 and GPR30.
Figure 12: Integral and peripheral proteins
Peripheral membrane proteins:
They are also called as extrinsic proteins; they do not interact with hydrophobic core of the membrane phospholipid bilayer. They are bound to the membrane by interaction with the intergral proteins or are bound to the bilayer' outer lipids polar heads groups. They are only present in the cytosolic region of the cell membrane. They play an important role in signal transduction. Some peripheral proteins are localized to the surface of the plasma membrane, these are called exoplasmic proteins. Peripheral enzymes are involved in the synthesis of different membrane components likeÂ lipidsÂ , cell wallÂ oligosaccharidesÂ , or proteins.
Membrane peripheral proteins are of five types: Structural proteins, channel proteins, transport or carrier proteins, enzymes and receptor proteins.
Carbohydrates are attached to membrane lipids and proteins as short oligosaccharide chains. Proteins attached with sugar molecules are called glycoproteins and lipids attached with sugar molecules are called glycolipids. The carbohydrates form a protective coat called glycocalyx around the cell, which helps in cell recognition.
Glycoproteins are formed by glycosylation of proteins. There are two types: N-glycosylation (sugar links to nitrogen atom of asparagines residue) and O-glycosylation (sugar attaches to hydroxyl group of serine or threonine rsidues). Examples of glycoproteins found in the body areÂ mucins, collagens, transferrins, immunogloulins, etc.
Glycolipids are lipids linked to oligosaccharide chains. Examples include glycosphingolipidsÂ which contain a hydrophobic ceramide,Â Â N-acylsphingosineÂ and saccharides. They are generally located on the outer membrane surface. The composition of the carbohydrate chain depends on the type of the cell and development of the organism.
 Chay, Lee, Fan, 1995
Appearance of Phase-locked Wenchbach-like Rhythms, Devil's Staircase and Universality in Intracellular Calcium Spikes in Non-excitable Cell Models
 The Fluid Mosaic Model of the Structure of Cell Membranes Cell membranes are viewed as two-dimensional solutions of oriented globular proteins and lipids. S. J. Singer and Garth L. Nicolson
 Â Krause J. William (July 2005).Â KrauseHYPERLINK "http://books.google.com/books?id=cRayoldYrcUC&pg=PA37"'HYPERLINK "http://books.google.com/books?id=cRayoldYrcUC&pg=PA37"s Essential Human Histology for Medical Students. Universal-Publishers. pp.Â 37-.Â ISBNÂ 9781581124682. Retrieved 25 November 2010.
 ] Glycosphingolipid functions: insights from engineered mouse models, doi: 10.1098/rstb.2003.1268
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Gap junction pic:
cell membrane pic