12.1 Phospholipids and Glycolipids Form Bimolecular Sheets

✓ 1 Identify the energetic force that powers the formation of membranes.

Figure 12.1: A section of phospholipid bilayer membrane. (A) Electron micrograph. (B) Space-filling model of an idealized view showing regular structures.

Recall from our earlier examination of membrane lipids that, although the repertoire of lipids is extensive, these lipids possess common structural elements: they are amphipathic molecules with a hydrophilic (polar) head group and a hydrophobic hydrocarbon tail. Membrane formation is a consequence of the amphipathic nature of the molecules. Their polar head groups favor contact with water, whereas their hydrocarbon tails interact with one another in preference to water. How can molecules with these preferences arrange themselves in aqueous solutions? The favored structure for most phospholipids and glycolipids in aqueous media is a lipid bilayer, composed of two lipid sheets. The hydrophobic tails of each individual sheet interact with one another, forming a hydrophobic interior that acts as a permeability barrier. The hydrophilic head groups interact with the aqueous medium on each side of the bilayer. The two opposing sheets are called leaflets (Figure 12.1).

Lipid bilayers form spontaneously by a self-assembly process. In other words, the structure of a bimolecular sheet is inherent in the structure of the constituent lipid molecules. The growth of lipid bilayers from phospholipids is rapid and spontaneous in water. The hydrophobic effect is the major driving force for the formation of lipid bilayers. Recall that the hydrophobic effect also plays a dominant role in the folding of proteins. Water molecules are released from the hydrocarbon tails of membrane lipids as these tails become sequestered in the nonpolar interior of the bilayer. Furthermore, van der Waals attractive forces between the hydrocarbon tails favor close packing of the tails. Finally, there are electrostatic and hydrogen-bonding attractions between the polar head groups and water molecules.

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Figure 12.2: A liposome. A liposome, or lipid vesicle, is a small aqueous compartment surrounded by a lipid bilayer.

!clinic! CLINICAL INSIGHT: Lipid Vesicles Can Be Formed from Phospholipids

The propensity of phospholipids to form membranes has been used to create an important experimental and clinical tool. Lipid vesicles, or liposomes, are aqueous compartments enclosed by a lipid bilayer (Figure 12.2). These structures can be used to study membrane permeability or to deliver chemicals to cells. Liposomes are formed by suspending a membrane lipid in an aqueous medium and then sonicating (i.e., agitating by high-frequency sound waves) to give a dispersion of closed vesicles that are quite uniform in size. Vesicles formed by this method are nearly spherical in shape and have a diameter of about 500 Å (50 nm). Ions or molecules can be trapped in the aqueous compartments of lipid vesicles if the vesicles are formed in the presence of these substances (Figure 12.3).

Figure 12.3: The preparation of glycine-containing liposomes. Liposomes containing glycine are formed by the sonication of phospholipids in the presence of glycine. Free glycine is removed by filtration.

Experiments are underway to develop clinical uses for liposomes. DNA-containing liposomes are currently being tested in more than 100 clinical trials for a variety of diseases. Liposomes may also contain drugs that can counter various pathological conditions. These liposomes fuse with the plasma membrane of many kinds of cells, introducing into the cells the molecules that they contain. The advantage of drug delivery by liposomes is that the drugs are more targeted than are systemic drugs, which means that less of the body is exposed to potentially toxic drugs. Liposomes are especially useful in targeting tumors and sites of inflammation, which have a high density of blood vessels. Liposomes concentrate in such areas of increased blood circulation, reducing the amount of drugs delivered to normal tissue. Currently, the largest use of liposomes is in the personal care industry where they are added to lotions and creams to deliver vitamins and other chemicals that are claimed to rejuvenate the skin.

Lipid Bilayers Are Highly Impermeable to Ions and Most Polar Molecules

✓ 2 Explain why membranes are impermeable to most substances.

The results of permeability studies of lipid bilayers have shown that lipid bilayer membranes have a very low permeability for ions and most polar molecules. The ability of molecules to move through a lipid environment, such as a membrane, is quite varied (Figure 12.4). For example, Na+ and K+ traverse these membranes 109 times more slowly than H2O. Tryptophan, a zwitterion at pH 7, crosses the membrane 103 times more slowly than indole, a structurally related molecule that lacks ionic groups. In fact, experiments show that the permeability of small molecules is correlated with their relative solubilities in water and nonpolar solvents. This relation suggests that a small molecule might traverse a lipid bilayer membrane in the following way: first, it sheds the water with which it is associated, called the solvation shell; then, it dissolves in the hydrocarbon core of the membrane; and, finally, it diffuses through this core to the other side of the membrane, where it is resolvated by water. An ion such as Na+ cannot cross the membrane, because the replacement of its shell of polar water molecules by nonpolar interactions with the membrane interior is highly unfavorable energetically.

Figure 12.4: Permeability coefficients of ions and molecules in a lipid bilayer. The ability of molecules to cross a lipid bilayer spans a wide range of values. The permeability coefficient P, expressed in cm s−1, provides a quantitative estimate of the rate of passage of a molecule across a membrane.

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