The Formation of a Phospholipid Bilayer
The cell membrane, also known as the plasma membrane, has been extensively studied and has significantly contributed to our understanding of membrane structure. Among all cell membranes, the plasma membrane of mammalian red blood cells (erythrocytes) has served as a valuable model for studying membrane structure. These cells lack nuclei or internal membranes, making it easy to isolate pure plasma membranes for biochemical analysis. Research on the red blood cell plasma membrane was pivotal in revealing that biological membranes consist of lipid bilayers. In 1925, two Dutch scientists, E. Gorter and R. Grendel, extracted membrane lipids from a specific number of red blood cells, corresponding to a known surface area of the plasma membrane. They then determined the surface area occupied by a monolayer of the extracted lipid spread out at an air-water interface. Surprisingly, the surface area of the lipid monolayer was twice that occupied by the erythrocyte plasma membranes, leading to the conclusion that membranes consist of lipid bilayers instead of monolayers.
The bilayer structure of the erythrocyte plasma membrane is clearly visible in high-resolution electron micrographs (Figure 12.1). The plasma membrane appears as two dense lines with an intervening space, resembling a “railroad track.” This appearance is due to the binding of heavy metals used as stains in transmission electron microscopy to the polar head groups of the phospholipids. These head groups appear as dark lines, while the hydrophobic fatty acid chains are lightly stained, creating the separation between the dense lines.
As discussed in Chapter 2, animal cell plasma membranes primarily contain four major phospholipids: phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, and sphingomyelin. These phospholipids make up more than half of the lipid composition in most membranes. Interestingly, the distribution of these phospholipids is asymmetrical between the two halves of the membrane bilayer (Figure 12.2). The outer leaflet of the plasma membrane mainly consists of phosphatidylcholine and sphingomyelin, while phosphatidylethanolamine and phosphatidylserine dominate the inner leaflet. Another phospholipid, phosphatidylinositol, is primarily found in the inner half of the plasma membrane. Although phosphatidylinositol is a minor component, it plays a crucial role in cell signaling, as discussed in the next chapter. Both phosphatidylserine and phosphatidylinositol carry a negative charge on their head groups, resulting in a net negative charge on the cytosolic face of the plasma membrane.
Glycolipids and cholesterol are also present in animal cell plasma membranes. Glycolipids are exclusively found in the outer leaflet of the plasma membrane, with their carbohydrate portions exposed on the cell surface. They constitute only a small fraction of the membrane lipids, about 2% in most cases. On the other hand, cholesterol is a major component of animal cell membranes and exists in similar molar amounts as phospholipids.
Two critical features of phospholipid bilayers are crucial for proper membrane function. Firstly, the structure of phospholipids forms a barrier between two aqueous compartments. The presence of hydrophobic fatty acid chains in the interior of the bilayer makes the membrane impermeable to water-soluble molecules such as ions and most biological molecules. Secondly, naturally occurring phospholipid bilayers are not solid but rather viscous fluids. This fluidity is due to the presence of one or more double bonds in the fatty acids of most natural phospholipids, introducing kinks into the hydrocarbon chains and preventing tight packing. Consequently, the fatty acids within the membrane can move freely, making the membrane soft and flexible. Both phospholipids and proteins can also diffuse laterally within the membrane, which is essential for various membrane functions.
Cholesterol, with its rigid ring structure, plays a distinct role in membrane structure. Although it cannot form a membrane by itself, cholesterol inserts into phospholipid bilayers with its polar hydroxyl group close to the phospholipid head groups. Depending on the temperature, cholesterol has different effects on membrane fluidity. At high temperatures, cholesterol hinders the movement of phospholipid fatty acid chains, reducing the fluidity and permeability of the outer part of the membrane. At low temperatures, however, cholesterol prevents membranes from freezing by disrupting interactions between fatty acid chains, thereby maintaining membrane fluidity. While bacteria do not contain cholesterol, it is an essential component of animal cell plasma membranes. Plant cells lack cholesterol but possess related compounds known as sterols, which serve a similar function.
Recent studies suggest that not all lipids diffuse freely within the plasma membrane. Instead, specific membrane domains enriched in cholesterol and sphingolipids (sphingomyelin and glycolipids) seem to exist. These lipid clusters, known as “rafts,” laterally move within the plasma membrane and may associate with specific membrane proteins. Although the exact functions of lipid rafts are still not fully understood, they likely play significant roles in cell signaling and the internalization of extracellular molecules through endocytosis.
