100,000. (Courtesy of Dr. Ray C. Henrikson.) membrane by strong ionic interactions, mainly with integral proteins on both the extracellular and intracellular surfaces of the membrane (see Fig. 2.3). In addition, on the extracellular surface of the plasma membrane, carbohydrates may be attached to proteins, thereby forming glycoproteins; or to lipids of the bilayer, thereby forming glycolipids. These surface molecules constitute a layer at the surface of the cell, referred to as the cell coat or glycocalyx (see Fig. 2.2). They help establish extracellular microenvironments at the membrane surface that have specific functions in metabolism, cell recognition, and cell association and serve as receptor sites for hormones.
Microdomains of the plasma membrane, known as lipid rafts, control the movement and distribution of proteins within the lipid bilayer.
The ﬂuidity of the plasma membrane is not revealed in static electron micrographs. Experiments reveal that the membrane behaves as though it were a two-dimensional lipid ﬂuid. For many years it was thought that integral membrane proteins moved freely within the plane of the membrane; this movement was compared to the movement of icebergs ﬂoating in the ocean (see Fig. 2.3). However, recent evidence shows that the distribution and movement of proteins within the lipid bilayer is not as random as once thought. Localized regions within the plasma membrane contain high concentrations of cholesterol and glycosphingolipids. These regions are called lipid rafts. Owing to the high concentration of cholesterol and the presence of longer, highly saturated fatty-acid chains, the lipid raft area is thicker and exhibits less ﬂuidity than the surrounding plasma membrane (Fig. 2.4). Lipid rafts contain a variety of integral and peripheral membrane proteins involved in cell signaling. They can be viewed as “signaling platforms” ﬂoating in the ocean of lipids. Each individual raft is equipped with all of the necessary elements (receptors, coupling factors, effector enzymes, and substrates) to receive and convey specific signals. Signal transduction in lipid rafts occurs more rapidly and efficiently because of the close proximity of interacting proteins. In addition, different signaling rafts allow for the separation of specific signaling molecules from each other.
Integral membrane proteins can be visualized with the special tissue preparation technique of freeze fracture.
The existence of protein within the substance of the plasma membrane (i.e., integral proteins) was confirmed by a technique called freeze fracture. When tissue is prepared for electron microscopy by the freeze fracture process (Fig. 2.5a), membranes typically split or cleave along the hydrophobic plane (i.e., between the two lipid layers) to expose two interior faces of the membrane, an E-face and a P-face (see Fig. 2.5b).
The E-face is backed by extracellular space, whereas the  P-face is backed by cytoplasm ( protoplasm). The numerous particles seen on the Eand P-faces with the TEM represent the integral proteins of the membrane. Usually, the P-face displays more particles, thus more protein, than the E-face (see Fig. 2.5c).
Integral membrane proteins have important functions in cell metabolism, regulation, and integration.
Six broad categories of membrane proteins have been defined in terms of their function: pumps, channels, receptors, linkers,