May 10, 2010

Membrane Structure

The plasma membrane is the edge of life, the boundary that separates the living cell from its nonliving surroundings. A remarkable film only about 8 nm thick—it would take over 8,000 to equal the thickness of this page—the plasma membrane controls traffic into and out of the cell it surrounds. Like all biological membranes, the plasma membrane exhibits selective permeability; that is, it allows some substances to cross it more easily than others. One of the earliest episodes in the evolution of life may have been the formation of a membrane that enclosed a solution different from the surrounding solution while still permitting the uptake of nutrients and elimination of waste products. This ability of the cell to discriminate in its chemical exchanges with its environment is fundamental to life, and it is the plasma membrane and its component molecules that make this selectivity possible.

Phospholipid bilayer cross section

More than 50 kinds of proteins have been found so far in the plasma membrane of red blood cells, for example. Phospholipids form the main fabric of the membrane, but proteins determine most of the membrane’s specific functions. Different types of cells contain different sets of membrane proteins, and the various membranes within a cell each have a unique collection of proteins.

Synthesis of membrane components and their orientation on the resulting membrane. The plasma membrane has distinct cytoplasmic and extracellular sides, or faces, with the extracellular face arising from the inside face of ER, Golgi, and vesicle membranes.

Membranes have distinct inside and outside faces. The two lipid layers may differ in specific lipid composition, and each protein has directional orientation in the membrane. When a vesicle fuses with the plasma membrane, the outside layer of the vesicle becomes continuous with the cytoplasmic layer of the plasma membrane. Therefore, molecules that start out on the inside face of the ER end up on the outside face of the plasma membrane.

The process starts with (1) the synthesis of membrane proteins and lipids in the endoplasmic reticulum. Carbohydrates (green) are added to the proteins (purple), making them glycoproteins. The carbohydrate portions may then be modified. (2) Inside the Golgi apparatus, the glycoproteins undergo further carbohydrate modification, and lipids acquire carbohydrates, becoming glycolipids. (3) Transmembrane proteins (purple dumbbells), membrane glycolipids, and secretory proteins (purple spheres) are transported in vesicles to the plasma membrane. (4) There the vesicles fuse with the membrane, releasing secretory proteins from the cell. Vesicle fusion positions the carbohydrates of membrane glycoproteins and glycolipids on the outside of the plasma membrane. Thus, the asymmetrical distribution of proteins, lipids, and their associated carbohydrates in the plasma membrane is determined as the membrane is being built by the ER and Golgi apparatus.

The biological membrane is an exquisite example of a supramolecular structure—many molecules ordered into a higher level of organization—with emergent properties beyond those of the individual molecules. The remainder of this chapter focuses on one of the most important of those properties: the ability to regulate transport across cellular boundaries, a function essential to the cell’s existence. We will see once again that form fits function: The fluid mosaic model helps explain how membranes regulate the cell’s molecular traffic.

A steady traffic of small molecules and ions moves across the plasma membrane in both directions. Consider the chemical exchanges between a muscle cell and the extracellular fluid that bathes it. Sugars, amino acids, and other nutrients enter the cell, and metabolic waste products leave it. The cell takes in oxygen for cellular respiration and expels carbon dioxide. It also regulates its concentrations of inorganic ions, such as Na+, K+, Ca2+, and Cl−, by shuttling them one way or the other across the plasma membrane. Although traffic through the membrane is extensive, cell membranes are selectively permeable, and substances do not cross the barrier indiscriminately. The cell is able to take up many varieties of small molecules and ions and exclude others. Moreover, substances that move through the membrane do so at different rates.

Hydrophobic (nonpolar) molecules, such as hydrocarbons, carbon dioxide, and oxygen, can dissolve in the lipid bilayer of the membrane and cross it with ease, without the aid of membrane proteins. However, the hydrophobic core of the membrane impedes the direct passage of ions and polar molecules, which are hydrophilic, through the membrane. Polar molecules such as glucose and other sugars pass only slowly through a lipid bilayer, and even water, an extremely small polar molecule, does not cross very rapidly. A charged atom or molecule and its surrounding shell of water find the hydrophobic layer of the membrane even more difficult to penetrate. Fortunately, the lipid bilayer is only part of the story of a membrane’s selective permeability. Proteins built into the membrane play key roles in regulating transport.

Cell membranes are permeable to specific ions and a variety of polar molecules. These hydrophilic substances can avoid contact with the lipid bilayer by passing through transport proteins that span the membrane. Some transport proteins, called channel proteins, function by having a hydrophilic channel that certain molecules or atomic ions use as a tunnel through the membrane. For example, the passage of water molecules through the membrane in certain cells is greatly facilitated by channel proteins known as aquaporins . Other transport proteins, called carrier proteins, hold onto their passengers and change shape in a way that shuttles them across the membrane. In both cases, the transport protein is specific for the substance it translocates (moves), allowing only a certain substance (or substances) to cross the membrane. For example, glucose carried in blood and needed by red blood cells for cellular activities enters these cells rapidly through specific transport proteins in the plasma membrane. This “glucose transporter” is so selective as a carrier protein that it even rejects fructose, a structural isomer of glucose.

Thus, the selective permeability of a membrane depends on both the discriminating barrier of the lipid bilayer and the specific transport proteins built into the membrane. But what determines the direction of traffic across a membrane? At a given time, will a particular substance enter or leave the cell? And what mechanisms actually drive molecules across membranes? We will address these questions next as we explore two modes of membrane traffic: passive transport and active transport.