Lipids are water insoluble biomolecules that are highly soluble in organic solvents such as chloroform. The three major kinds of membrane lipids are phospholipids, glycolipids, and cholesterol. Lipids are amphiphilic: they have one end that is soluble in water (‘polar’) and an ending that is soluble in fat (‘nonpolar’).
Biological membranes usually involve two layers of phospholipids with their tails pointing inward, an arrangement called a phospholipid bilayer.
A phospholipid is a lipid made of glycerol ( a 3- carbon alcohol), or sphingosine (a more complex alcohol), two fatty acid tails, and a phosphate-linked head group. The hydrophilic, or “water-loving,” portion of a phospholipid is its head, which contains a negatively charged phosphate group as well as an additional small group (of varying identity, “R”), which may also or be charged or polar. The hydrophilic heads of phospholipids in a membrane bilayer face outward, contacting the aqueous (watery) fluid both inside and outside the cell. Since water is a polar molecule, it readily forms electrostatic (charge-based) interactions with the phospholipid heads.
The hydrophobic, or “water-fearing,” part of a phospholipid consists of its long, nonpolar fatty acid tails. The fatty acid tails can easily interact with other nonpolar molecules, but they interact poorly with water. Because of this, it’s more energetically favorable for the phospholipids to tuck their fatty acid tails away in the interior of the membrane, where they are shielded from the surrounding water. The phospholipid bilayer formed by these interactions makes a good barrier between the interior and exterior of the cell, because water and other polar or charged substances cannot easily cross the hydrophobic core of the membrane.
Phospholipids derived from glycerol are called phosphoglycerides. A phosphoglyceride consists of a glycerol backbone to which two fatty acid chains and a phosphorylated alcohol are attached. In phosphoglycerides, the hydroxyl groups at C-1 and C-2 of glycerol are esterified to the carboxyl groups of the two fatty acid chains. The C-3 hydroxyl group of the glycerol backbone is esterified to phosphoric acid. When no further additions are made, the resulting compound is phosphatidate (diacylglycerol 3-phosphate), the simplest phosphoglyceride. Only small amounts of phosphatidate are present in membranes. However, the molecule is a key intermediate in the biosynthesis of the other phosphoglycerides. The major phosphoglycerides are derived from phosphatidate by the formation of an ester bond between the phosphate group of phosphatidate and the hydroxyl group of one of several alcohols. The common alcohol moieties of phosphoglycerides are the amino acid serine, ethanolamine, choline, glycerol, and the inositol.
The plasma membranes of animal cells contain four major phospholipids : phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, and sphingomyelin, which together account for more than half of the lipid in most membranes. These phospholipids are asymmetrically distributed between the two halves of the membrane bilayer.
The outer leaflet of the plasma membrane consists mainly of phosphatidylcholine and sphingomyelin, whereas phosphatidylethanolamine and phosphatidylserine are the predominant phospholipids of the inner leaflet. A fifth phospholipid, phosphatidylinositol, is also localized to the inner half of the plasma membrane. Although phosphatidylinositol is a quantitatively minor membrane component, it plays an important role in cell signaling. The head groups of both phosphatidylserine and phosphatidylinositol are negatively charged, so their predominance in the inner leaflet results in a net negative charge on the cytosolic face of the plasma membrane.
Glycolipids are lipids with a carbohydrate attached by a glycosidic bond. Their role is to maintain stability of the membrane and to facilitate cellular recognition. The carbohydrates are found on the surface of all eukaryotic cell membranes. They extend from the phospholipid bilayer into the extracellular, aqueous environment.
The basic structure of a glycolipid is the presence of a carbohydrate monosaccharide or oligosaccharide bound to a lipid moiety. The lipid complex most often comprises either a glycerol or a sphingosine backbone, which engenders glyceroglycolipids and sphingolipids, the two main categories of glycolipids.
As non-polar molecules, lipids are able to interact with the lipid-bilayer of the cell membrane and to anchor the glycolipid to the surface of the cell. Carbohydrates are used as the ligand components of glycolipids, and their structure varies depending on the structure of the molecule to which they bind. The carbohydrate contains polar groups that enable the molecule to be soluble in the aqueous environment surrounding the cell.
Cholesterol, is a steroid composed of four fused carbon rings and a small polar head group, found alongside phospholipids in the core of the membrane.
A hydrocarbon tail is linked to the steroid at one end, and a hydroxyl group is attached at the other end. In membranes, the molecule is oriented parallel to the fatty acid chains of the phospholipids, and the hydroxyl group interacts with the nearby phospholipid head groups. Cholesterol is absent from prokaryotes but is found to varying degrees in virtually all animal membranes. It constitutes almost 25% of the membrane lipids in certain nerve cells but is essentially absent from some intracellular membranes.
Cholesterol plays an important role in regulating the properties of phospholipid membranes. It changes the fluidity, thickness, compressibility, water penetration and intrinsic curvature of lipid bilayers.
Due to steric reasons, cholesterol prevents two phospholipid molecules from coming too close to each other (especially prevents freezing when the temperature is low) and hence prevents the plasma membrane from becoming rigid. So, it maintains the fluidity. Also, the polar -OH groups of the cholesterol interact with the polar head groups of the phospholipids and hold the membrane together. At high temperatures too, they attract each other and prevent the membrane from breaking down. Hence maintaining the stability of the membrane.
Amphipathic Lipids Aggregate
When mixed with water, these amphipathic compounds form microscopic lipid aggregates in a phase separate from their aqueous surroundings. Lipid molecules cluster together with their hydrophobic moieties in contact with each other and their hydrophilic groups interacting with the surrounding water. Lipid clustering reduces the amount of hydrophobic surface exposed to water and thus minimizes the number of molecules in the shell of ordered water at the lipid-water interface, resulting in an increase in entropy. Hydrophobic interactions among lipid molecules provide the thermodynamic driving force for the formation and maintenance of these structures.
Depending on the precise conditions and the nature of the lipids used, three types of lipid aggregates can form when amphipathic lipids are mixed with water.
Micelles are relatively small, spherical structures involving a few dozen to a few thousand molecules arranged so that their hydrophobic regions aggregate in the interior, excluding water, and their hydrophilic head groups are at the surface, in contact with water. Micelle formation is favored when the cross sectional area of the head group is greater than that of the acyl side chain(s) ( if the phospholipids have small tails), as it is in free fatty acids, lysophospholipids (which lack one fatty acid), and the detergent SDS.
A second type of lipid aggregate in water is the bilayer, in which two lipid monolayers combine to form a two-dimensional sheet. Bilayer formation occurs most readily when the cross-sectional areas of the head group and side chain(s) are similar, as in glycerophospholipids and sphingolipids. The hydrophobic portions in each monolayer interact, excluding water. The hydrophilic head groups interact with water at the two surfaces of the bilayer.
The third type of lipid aggregate is formed when a lipid bilayer folds back on itself (if they have bulkier tails) to form a hollow sphere called a liposome or vesicle . By forming vesicles, bilayer sheets lose their hydrophobic edge regions, achieving maximal stability in their aqueous environment. These bilayer vesicles enclose water, creating a separate aqueous compartment. It is likely that the first living cells resembled liposomes, their aqueous contents segregated from the rest of the world by a hydrophobic shell.