Many plasma membrane proteins function together as larger complexes; these may assemble under the control of chaperone molecules in the RER or by lateral diffusion in the plasma membrane. The latter mechanism is characteristic of many protein receptors (e.g., cytokine receptors) that dimerize or trimerize in the presence of ligand to form functional signaling units. Although lipid bilayers are fluid in the two-dimensional plane of the membrane, membrane components can nevertheless be constrained to discrete domains. This can occur by localization to lipid rafts (discussed earlier), or through intercellular protein–protein interactions (e.g., at tight junctions) that establish discrete boundaries; indeed, this strategy is used to maintain cell polarity (e.g., top/apical versus bottom/basolateral) in epithelial layers. Alternatively, unique domains can be formed through the interaction of membrane proteins with cytoskeletal molecules or an extracellular matrix (ECM).
The extracellular face of the plasma membrane is diffusely studded with carbohydrates, not only as complex oligosaccharides on glycoproteins and glycolipids, but also as polysaccharide chains attached to integral membrane proteoglycans. This glycocalyx functions as a chemical and mechanical barrier, and is also involved in cell–cell and cell–matrix interactions.
Small, nonpolar molecules such as O2 and CO2 readily dissolve in lipid bilayers and therefore rapidly diffuse across them, as do hydrophobic molecules (e.g., steroid-based molecules such as estradiol or vitamin D). Similarly, small polar molecules (<75 daltons in mass, such as water, ethanol, and urea) readily cross membranes. In contrast, the lipid bilayer is an effective barrier to the passage of larger polar molecules, even those only slightly greater than 75 daltons, such as glucose. Lipid bilayers also are impermeant to ions, no matter how small, because of their charge and high degree of hydration. We will next discuss specialized mechanisms that regulate traffic across plasma membranes.
For each of the larger polar molecules that must cross membranes to support normal cellular functions (e.g., for nutrient uptake and waste disposal), unique plasma membrane protein complexes are typically required. For low-molecular-weight species (ions and small molecules up to approximately 1000 daltons), channel proteins and carrier proteins may be used (although this discussion focuses on plasma membranes, it should be noted that similar pores and channels are needed for transport across organellar membranes). Each transported molecule (e.g., ion, sugar, nucleotide) requires a transporter that is typically highly specific (e.g., glucose but not galactose):
Channel proteins create hydrophilic pores that, when open, permit rapid movement of solutes (usually restricted by size and charge;
Fig. 1.8
Carrier proteins bind their specific solute and undergo a series of conformational changes to transfer the ligand across the membrane; their transport is relatively slow.
In many cases, a concentration and/or electrical gradient between the inside and outside of the cell drives solute movement via passive transport (virtually all plasma membranes have an electrical potential difference across them, with the inside negative relative to the outside). In other cases, active transport of certain solutes against a concentration gradient is accomplished by carrier molecules (not channels) using energy released by ATP hydrolysis or a coupled ion gradient. Transporter ATPases include the notorious multidrug resistance (MDR) protein, which pumps polar compounds (e.g., chemotherapeutic drugs) out of cells and may render cancer cells resistant to treatment.