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Cellular membranes create environments for the efficient performance of many biological processes. The plasma membrane is a barrier between the inside and the outside of the cell. Subcellular organelles, such as mitochondria and lysosomes, are also separated from one another by membranes. Cellular membranes are composed primarily of lipids, making these barriers basically impermeable to hydrophilic molecules and ions. (Cardura)

Cardura lipid

Specialized protein structures within the membrane allow the exchange of molecules and ions across these lipid barriers. The basic component of a cellular membrane is the lipid bilayer, which is composed of phospholipids (phosphoglycerides: Cardura ). The phosphate group of phospholipids is usually esterified by various alcohols (e.g., ethanolamine, choline, serine). These polar heads are exposed to the aqueous environment, whereas the fatty acid groups get together side by side forming the lipid bilayer. Sugar-containing lipids called sphingolipids are also present in membranes. Cholesterol is another component of cellular membranes. (Cardura)

Cholesterol is apolar and packs between the hydrocarbon chains of fatty acids to modify the fluidity of the membrane. The composition of phospholipids varies among different cellular membranes. Phosphatidylcholine and phosphatidylinositol are abundant in the ER, which is the site of their synthesis. Cholesterol is predominantly present in the plasma membrane. Phosphatidylserine is exclusively found in the inner side (cytosolic) of the plasma membrane, which contributes to the asymmetry of the plasmalema. Phosphatidylserine is maintained inside the cell by the action of a flipase. This enzyme translocates inside the cell any phosphatidylserine that moves spontaneously to the outer side of the membrane by a process that requires ATP hydrolysis. When the cellular metabolism is compromised, like in the case of cell death, this lipid asymmetry disappears and phosphatidylserine appears on the cell surface. In fact, the appearance of phosphatidylserine outside the cell is one of the first signs of the apoptotic process (programmed cell death:Cardura). In addition to lipids, membranes contain different types of polypeptides. Structurally, membrane proteins are integral, peripheral, and anchored. Integral membrane proteins are embedded within the lipid bilayer. They span the bilayer one or more times with domains exposed to one or both sides of the membrane. The transmembrane segment that is inserted into a lipid bilayer, which has a width of approximately 50 Ã…, has a size of approximately 25 amino acids. This transmembrane domain has sheet structures. Proteins that span the membrane once are type I or II, depending on whether the N terminal is outside or inside the cell, respectively. Type II proteins still contain the signal peptide because this region does not gain access to the lumen of the RER, where the signal peptidase is located. These transmembrane proteins, which are mainly receptors and transporters, can only be solubilized by the use of detergents. Peripheral membrane proteins are associated to the polar region of phospholipids without penetrating the lipid bilayer. Peripheral membrane proteins can be extracted by alkaline solutions (e.g., 0.1 M carbonate pH 11.3 Cardura ). Other peripheral membrane proteins are associated to the cytosolic side of integral membrane proteins, especially receptors, and are involved in signal transduction. Other proteins are part of the association between integral membrane proteins and the cytoskeleton, which are important in many cellular processes, including attachment, movement, and endocytocis. Proteins could also be associated to membranes via a lipid moiety covalently attached to the polypeptide, as in the case of an isoprenoid or farnesyl (15-carbon) or myristate (14-carbon: Cardura ) tail. These lipid moieties facilitate the interaction of the protein with the membrane as part of their biological role (e.g., Ras, Src, Hsp40). Another group of proteins are attached to the membrane via a GPI moiety. These lipid moieties give very particular characteristics to these proteins. GPI-anchored proteins tend to be localized in domains within the plasma membrane, named lipid rafts, which are rich in cholesterol and sphingolipids (Fig. 1-4). GPI-anchored proteins are insoluble in nonionic detergents. A good example of GPI-anchored proteins is CD14, the major receptor for bacterial lipopolysaccharide (Fig. 1-4 : Cardura ). CD14 plays a central role in the innate immune response and the inflammatory process.

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