As previously mentioned, lipid rafts containing integral membrane proteins may move to a different region of the plasma membrane. The movement of an integral protein anchored on a lipid raft makes signaling more precise and prevents nonspecific interactions. The lateral migration of proteins is often limited by physical connections between membrane proteins and intracellular or extracellular structures. Such connections may exist between:  proteins associated with cytoskeletal elements and portions of the membrane proteins that extend into the adjacent cytoplasm, the cytoplasmic domains of membrane proteins, and  peripheral proteins associated with the extracellular matrix and the integral membrane proteins that extend from the cell surface (i.e., the extracellular domain).
Through these connections, proteins can be localized or restricted to specialized regions of the plasma membrane or act as transmembrane linkers between intracellular and extracellular filaments (see the next section).
Cell injury often manifests as morphologic changes in the cell’s plasma membrane, which results in the formation of plasma-membrane blebs. These are dynamic cell protrusions of the plasma membrane that are commonly observed in acute cell injury, in dividing and dying cells, and during cell movement. Blebbing is caused by the detachment of the plasma membrane from underlying actin flaments of the cell cytoskeleton. Cytoskeletal poisons that act on actin flaments such as phalloidin and cytochalasin-B cause extensive membrane blebbing.
Substances that enter or leave the cell must traverse the plasma membrane.
Some substances (fat-soluble and small, uncharged molecules) cross the plasma membrane by simple diffusion down their concentration gradient (Fig. 2.7a). All other molecules require membrane transport proteins to provide them with indi vidual passage across the plasma membrane. There are generally two classes of transport proteins:  Carrier proteins transfer small, water-soluble molecules. They are highly selective, often transporting only one type of molecule. After binding to a molecule designated for transport, the carrier protein undergoes a series of conformational changes and releases the molecule on the other side of the membrane (Fig. 2.7b). Some carrier proteins, such as the Na /K pump or H pump, require energy for active transport of molecules against their concentration gradient. Other carrier proteins, such as glucose carriers, do not require energy and participate in passive transport.
 Channel proteins also transfer small, water-soluble molecules. In general, channels are made of transmembrane proteins with several membrane-spanning domains that create hydrophilic channels through the plasma membrane. Usually, channel proteins contain a pore domain that partially penetrates the membrane bilayer and serves as the ionselectivity filter. The pore domain is responsible for exquisite ion selectivity, which is achieved by regulation of its three-dimensional structure (Fig. 2.7c). Channels are ion selective and are regulated on the basis of the cell’s needs. Channel protein transport can be regulated by membrane potentials (e.g., voltage-gated ion channels in neurons), neurotransmitters (e.g., ligand-gated ion channels such as acetylcholine receptors in