All biological membranes contain proteins. Typically, cell membranes have 1 protein molecule for every 25 lipid molecules. This ratio varies depending on membrane function. In the inner membrane of the mitochondrion, which is specialized for energy processing, there is 1 protein for every 15 lipids. However, myelin—a modified cell membrane that encloses portions of some neurons (nerve cells) and acts as an electrical insulator—has only 1 protein for every 70 lipids.

Membrane proteins are very diverse. In fact, about one-fourth of the protein-coding genes in the eukaryotic genome encode membrane proteins. There are two general types of membrane proteins: integral proteins and peripheral proteins.

Integral membrane proteins are at least partly embedded in the phospholipid bilayer (see Figure 6.1). Like phospholipids, these proteins have both hydrophilic and hydrophobic regions (domains) (Figure 6.3).

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Peripheral membrane proteins lack exposed hydrophobic groups and are not embedded in the bilayer. Instead, they have polar or charged regions that interact with exposed parts of integral membrane proteins, or with the polar heads of phospholipid molecules (see Figure 6.1).

A special preparation method for electron microscopy, called freeze-fracturing, reveals proteins that are embedded in the phospholipid bilayers of cellular membranes (Figure 6.4). When the two lipid leaflets (or layers) that make up the bilayer are separated, the proteins can be seen as bumps that protrude from the interior of each membrane. The bumps are not observed when artificial bilayers of pure lipid are freeze-fractured.

Membrane proteins and lipids generally interact only noncovalently. The polar ends of proteins can interact with the polar ends of lipids, and the nonpolar regions of both molecules can interact hydrophobically. As mentioned above, however, some membrane proteins have hydrophobic lipid components covalently attached to them that allow these proteins to tether themselves to the phospholipid bilayer.

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Proteins are asymmetrically distributed on the inner and outer surfaces of membranes. An integral protein that extends all the way through the phospholipid bilayer and protrudes on both sides is known as a transmembrane protein. In addition to one or more transmembrane domains that extend through the bilayer, such a protein may have domains with other specific functions on the inner and outer sides of the membrane. Peripheral membrane proteins, by contrast, are located on one side of the membrane or the other. This asymmetrical arrangement of membrane proteins gives the two surfaces of the membrane different properties. As you will soon see, these differences have great functional significance.

Like lipids, some membrane proteins move around relatively freely within the phospholipid bilayer. Experiments that involve the technique of cell fusion illustrate this migration dramatically. When two cells are fused, a single continuous membrane forms and surrounds both cells, and some proteins from each cell distribute themselves uniformly around this membrane (Figure 6.5).

Although some proteins are free to migrate in the membrane, others are not, but rather appear to be “anchored” to a specific region of the membrane. These membrane regions are like an enclosure of animals at the zoo: the animals are free to move around within the fenced area but not outside it. An example is the protein in the cell membrane of a muscle cell that recognizes a chemical signal from a neuron. This protein is normally found only at the specific region where the neuron meets the muscle cell. Proteins inside the cell can restrict the movement of proteins within a membrane. The cytoskeleton has components just below the inner face of the membrane that are attached to membrane proteins protruding into the cytoplasm. The stability of the cytoskeletal components may thus restrict movement of attached membrane proteins.