The cell membrane is made up of lipids, proteins mainly. Among the lipids, the phospholipid is the majority and the proteins which are present in the cell membrane perform a variety of functions and they are ion passage, cell signaling, signal transduction, etc.
Lipids present in the cell membrane
The phospholipids in the cell membrane are a structure that is mainly made of Phospholipids, Proteins, Cholesterol, and many other components.
(I) Phospholipids - Amphipathic (i.e they have two parts, one part can stay in the water and the other can stay outside water just like an amphibian, for example, a frog which stays inside water as a tadpole but evolves out of the water as it grows, hence the word amphipathic)
- A phospholipid is an umbrella term for a class of somewhat similar-looking compounds. - -Phospholipids, which are mainly present in the cell membrane are classified into 3 main types and they are – (a) Phosphoglycerides (b) Sphingolipids.
(a) Phosphoglycerides à these are the most abundant type of available phospholipids
in the cell membrane. A phosphoglyceride has 2 fatty acyl chains [-(CH2)n-] with 16 to 18 carbons in the chain, and a polar head. Interestingly the phosphoglycerides are categorized based on the type of polar head they have. If the polar molecule is choline, alcohol then the phosphoglyceride is called the phosphatidylcholine, if it is -OH containing alcohol like the ethanolamine, serine, inositol then they are given a name accordingly. In solution, the phosphatidylcholine and phosphatidylethanolamine have no net charge, but phosphatidylinositol and phosphatidylserine have a net negative charge due to their phosphate group.
Plasmalogens are a class of phospholipids that are special in the sense that carbon 1 of the glycerol is attached to the fatty acid chain by ether linkage and not by ester linkage. They are mainly found in the brain and cardiac tissue.
(b) Sphingolipids - In the case of sphingolipids the backbone is not glycerol but they are made of sphingosine (long-chain amino alcohol). As the sphingosine is having an amino group that’s why the fatty acids are attached to the alcohol backbone by the amide linkage and not by the ester linkage. Sphingolipids can be classified into two main types Sphingomyelins and glycolipids.
Sphingomyelin can form mixed bilayers as they are similar in structure concerning phospholipids. Glycolipids are especially used in the brain (neurons).
(II) Cholesterol - Cholesterol is absent in all prokaryotic cells but is present in all eukaryotic cells (both plant and animals). Almost 50 to 90 % of the cholesterol is present in the cell membrane. Cholesterol has a hydrophobic core structure and the hydrophilic fatty acid chains are connected to the -OH group present on the cholesterol molecule and this is how cholesteryl esters are formed. The introduction of cholesterol to the cell membrane is associated with the decrease in the fluidity of the cell membrane. Apart from their role in the cell membrane, cholesterol is also used in the making of bile acids, vitamin D, steroid hormones (estrogen, progesterone, testosterone, aldosterone, etc).
Now that we have discussed the main components of our cell membrane we must now discuss some important aspects of the cell membrane.
à Lateral movement of the Phospholipids à Within the cell membrane, the lipids are allowed to move i.e. the positions of the phospholipids is not permanent rather it changes from time to time. Phospholipids can move laterally over the whole surface of the cell membrane except few sites on the cell surface (called lipid rafts which are abundant in cholesterol). Application of heat to the bilayer causes the fatty acid chains to disrupt due to which the ‘gel-like constituency of the cell membrane’ is lost.
The transient lateral movement of the phospholipids is studied by a technique called the FRAP (Fluorescence Recovery After Photobleaching).
Lipid composition is not uniform throughout the cell membrane and also varies from organelle to organelle in the cell. The fluidity of the membrane depends on 2 things (i) fatty acid chains of the phospholipids (ii) composition of the membrane.
The fatty acids that make up the phospholipids are divided into three main categories based on their acyl chain length. Fatty acid chains that are long and do not have any double bond interact strongly with each other and thus the Vander Waal's forces and the hydrophobic interactions are strong in these lipids and thus they pack tightly and thus form a gel-like cell membrane. A fatty acid with shorter chains and no double bond has few Vander Waal's interactions and also few hydrophobic interactions and thus they form fluidic bilayers. Thus fatty acid chains with double bonds are less stable and thus they form less stable bilayers and thus fluidic bilayers and this is because due to the double bonds the hydrophobic interaction and the Vander Waal's interaction are weak.
Lipids structure and their position within the cell membrane à Cholesterol molecule increases bilayer thickness but decreases membrane fluidity. The thickness of a membrane with only Phosphatidylcholine is only 3.5mm but the addition of cholesterol to that causes the thickness to increase to 4mm. Membranes which are made up of the sphingomyelins do not affect the introduction of cholesterol on the thickness.
Lipids with large acyl chains (phosphatidylcholine) and the and polar heads are ‘barrel shaped’ and as a result the resulting cell membrane is flat. Lipids with small polar heads (phosphatidylethanolamine) have enough space for their acyl chains to stretch and thus these lipids become ‘conical’ in shape and these lipids are placed near the curves of the cell membrane.
Proteins associated with cell membrane
Proteins which are associated with the cell membrane are classified into two categories mainly
(i) proteins which are transmembrane and
(ii) proteins that are facing the cytosol and attached to the cell membrane lipids.
(iii) proteins that are attached to the external surface of the cell membrane
(i) Transmembrane proteins - Transmembrane proteins are present in specialized areas of the cell membrane called lipid rafts which have a high content of cholesterol thus restricting the transient movement of lipids in that particular patch of the cell membrane. The transmembrane helices of the proteins are made of alpha-helices which contain hydrophobic amino acids.
(ii) Proteins which are attached to the cytosolic face of the cell membrane à They were earlier called the intrinsic proteins but this type of nomenclature is not used today. The proteins which are attached to the lipids and face the cytosol of the cell have hydrophilic amino acids exposed to the cytosol and the hydrophobic amino acids are packed inside in the tertiary structure.
(iii) Proteins that are placed outside the cell membrane have an almost similar arrangement of the amino acids compared to the proteins that are present in the cytosolic face.
(Write up to this when you are asked about the composition of the cell membrane)
Phospholipid Bilayer disruption – the role of ‘detergents’
The cell membrane is disrupted for many reasons such as the study of the membrane proteins and the study of the proteins present in the cytoplasm. The cell membrane is disrupted by the application of detergents. Detergents are chemicals that have both hydrophilic and hydrophilic ends (that is they are amphipathic). Detergents having any charge (positive or negative) are called ionic detergents & neutral detergents are known as non-ionic detergents. Ionic detergents are SDS & an example of non-ionic detergent is Triton X100.
When do we use ionic detergents?
We use ionic detergents when we want to study only the primary structure of any protein because, after the application of ionic detergents, the tertiary and secondary structure of the protein is destroyed due to the presence of charge on the detergents.
When do we use non-ionic detergents?
We use non-ionic detergents when we want to extract the exact structure of the membrane-associated or cytoplasmic proteins for further study (for determining the 3D structure of a protein using X-ray crystallography) then we use a non-ionic detergent such as Triton-X 100.
References
1. Molecular Cell Biology 8Th Edn 2016 Edition by LODISH, FREEMAN MACMILLAN.
2. Biochemistry, 4Th Edition by Voet D, John Wiley
3. Weiwei Fan, Ronald M. Evans,Turning Up the Heat on Membrane Fluidity,Cell,Volume 161,Issue5,2015,Pages962963,ISSN00928674,https://doi.org/10.1016/j.cell.2015.04.046.
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