With few exceptions, cellular membranes — including plasma membranes and internal membranes — are made of glycerophospholipids, molecules composed of glycerol, a phosphate group, and two fatty acid chains. Glycerol is a three-carbon molecule that functions as the backbone of these membrane lipids. Within an individual glycerophospholipid, fatty acids are attached to the first and second carbons, and the phosphate group is attached to the third carbon of the glycerol backbone. Variable head groups are attached to the phosphate. Space-filling models of these molecules reveal their cylindrical shape, a geometry that allows glycerophospholipids to align side-by-side to form broad sheets (Figure 1).
Figure 1: The lipid bilayer and the structure and composition of a glycerophospholipid molecule
(A) The plasma membrane of a cell is a bilayer of glycerophospholipid molecules. (B) A single glycerophospholipid molecule is composed of two major regions: a hydrophilic head (green) and hydrophobic tails (purple). (C) The subregions of a glycerophospholipid molecule; phosphatidylcholine is shown as an example. The hydrophilic head is composed of a choline structure (blue) and a phosphate (orange). This head is connected to a glycerol (green) with two hydrophobic tails (purple) called fatty acids. (D) This view shows the specific atoms within the various subregions of the phosphatidylcholine molecule. Note that a double bond between two of the carbon atoms in one of the hydrocarbon (fatty acid) tails causes a slight kink on this molecule, so it appears bent.
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Glycerophospholipids are by far the most abundant lipids in cell membranes. Like all lipids, they are insoluble in water, but their unique geometry causes them to aggregate into bilayers without any energy input. This is because they are two-faced molecules, with hydrophilic (water-loving) phosphate heads and hydrophobic (water-fearing) hydrocarbon tails of fatty acids. In water, these molecules spontaneously align — with their heads facing outward and their tails lining up in the bilayer's interior. Thus, the hydrophilic heads of the glycerophospholipids in a cell's plasma membrane face both the water-based cytoplasm and the exterior of the cell.
Altogether, lipids account for about half the mass of cell membranes. Cholesterol molecules, although less abundant than glycerophospholipids, account for about 20 percent of the lipids in animal cell plasma membranes. However, cholesterol is not present in bacterial membranes or mitochondrial membranes. Also, cholesterol helps regulate the stiffness of membranes, while other less prominent lipids play roles in cell signaling and cell recognition.
Figure 2: The glycerophospholipid bilayer with embedded transmembrane proteins
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At physiological temperatures, cell membranes are fluid; at cooler temperatures, they become gel-like. Scientists who model membrane structure and dynamics describe the membrane as a fluid mosaic in which transmembrane proteins can move laterally in the lipid bilayer. Therefore, the collection of lipids and proteins that make up a cellular membrane relies on natural biophysical properties to form and function. In living cells, however, many proteins are not free to move. They are often anchored in place within the membrane by tethers to proteins outside the cell, cytoskeletal elements inside the cell, or both.
The structure and function of cells are critically dependent on membranes, which not only separate the interior of the cell from its environment but also define the internal compartments of eukaryotic cells, including the nucleus and cytoplasmic organelles. The formation of biological membranes is based on the properties of lipids, and all cell membranes share a common structural organization: bilayers of phospholipids with associated proteins. These membrane proteins are responsible for many specialized functions; some act as receptors that allow the cell to respond to external signals, some are responsible for the selective transport of molecules across the membrane, and others participate in electron transport and oxidative phosphorylation. In addition, membrane proteins control the interactions between cells of multicellular organisms. The common structural organization of membranes thus underlies a variety of biological processes and specialized membrane functions, which will be discussed in detail in later chapters.
Membrane Lipids
The fundamental building blocks of all cell membranes are phospholipids, which are amphipathic molecules, consisting of two hydrophobic fatty acid chains linked to a phosphate-containing hydrophilic head group (see ). Because their fatty acid tails are poorly soluble in water, phospholipids spontaneously form bilayers in aqueous solutions, with the hydrophobic tails buried in the interior of the membrane and the polar head groups exposed on both sides, in contact with water (). Such form a stable barrier between two aqueous compartments and represent the basic structure of all biological membranes.
Figure 2.45
A phospholipid bilayer. Phospholipids spontaneously form stable bilayers, with their polar head groups exposed to water and their hydrophobic tails buried in the interior of the membrane.
Lipids constitute approximately 50% of the mass of most cell membranes, although this proportion varies depending on the type of membrane. Plasma membranes, for example, are approximately 50% lipid and 50% protein. The inner membrane of mitochondria, on the other hand, contains an unusually high fraction (about 75%) of protein, reflecting the abundance of protein complexes involved in electron transport and oxidative phosphorylation. The lipid composition of different cell membranes also varies (). The plasma membrane of E. coli consists predominantly of phosphatidylethanolamine, which constitutes 80% of total lipid. Mammalian plasma membranes are more complex, containing four major phospholipids—phosphatidylcholine, phosphatidylserine, phosphatidylethanolamine, and sphingomyelin—which together constitute 50 to 60% of total membrane lipid. In addition to the phospholipids, the plasma membranes of animal cells contain glycolipids and cholesterol, which generally correspond to about 40% of the total lipid molecules.
Table 2.3
Lipid Composition of Cell Membranes a.
An important property of lipid bilayers is that they behave as two-dimensional fluids in which individual molecules (both lipids and proteins) are free to rotate and move in lateral directions (). Such fluidity is a critical property of membranes and is determined by both temperature and lipid composition. For example, the interactions between shorter fatty acid chains are weaker than those between longer chains, so membranes containing shorter fatty acid chains are less rigid and remain fluid at lower temperatures. Lipids containing unsaturated fatty acids similarly increase membrane fluidity because the presence of double bonds introduces kinks in the fatty acid chains, making them more difficult to pack together.
Figure 2.46
Mobility of phospholipids in a membrane. Individual phospholipids can rotate and move laterally within a bilayer.
Because of its hydrocarbon ring structure (see ), cholesterol plays a distinct role in determining membrane fluidity. Cholesterol molecules insert into the bilayer with their polar hydroxyl groups close to the hydrophilic head groups of the phospholipids (). The rigid hydrocarbon rings of cholesterol therefore interact with the regions of the fatty acid chains that are adjacent to the phospholipid head groups. This interaction decreases the mobility of the outer portions of the fatty acid chains, making this part of the membrane more rigid. On the other hand, insertion of cholesterol interferes with interactions between fatty acid chains, thereby maintaining membrane fluidity at lower temperatures.
Figure 2.47
Insertion of cholesterol in a membrane. Cholesterol inserts into the membrane with its polar hydroxyl group close to the polar head groups of the phospholipids.
Membrane Proteins
Proteins are the other major constituent of cell membranes, constituting 25 to 75% of the mass of the various membranes of the cell. The current model of membrane structure, proposed by Jonathan Singer and Garth Nicolson in 1972, views membranes as a fluid mosaic in which proteins are inserted into a lipid bilayer (). While phospholipids provide the basic structural organization of membranes, membrane proteins carry out the specific functions of the different membranes of the cell. These proteins are divided into two general classes, based on the nature of their association with the membrane. are embedded directly within the lipid bilayer. are not inserted into the lipid bilayer but are associated with the membrane indirectly, generally by interactions with integral membrane proteins.
Figure 2.48
Fluid mosaic model of membrane structure. Biological membranes consist of proteins inserted into a lipid bilayer. Integral membrane proteins are embedded in the membrane, usually via α-helical regions of 20 to 25 hydrophobic amino acids. Some (more...)
Many integral membrane proteins (called ) span the lipid bilayer, with portions exposed on both sides of the membrane. The membrane-spanning portions of these proteins are usually α-helical regions of 20 to 25 nonpolar amino acids. The hydrophobic side chains of these amino acids interact with the fatty acid chains of membrane lipids, and the formation of an α helix neutralizes the polar character of the peptide bonds, as discussed earlier in this chapter with respect to protein folding. Like the phospholipids, transmembrane proteins are amphipathic molecules, with their hydrophilic portions exposed to the aqueous environment on both sides of the membrane. Some transmembrane proteins span the membrane only once; others have multiple membrane-spanning regions. Most transmembrane proteins of eukaryotic plasma membranes have been modified by the addition of carbohydrates, which are exposed on the surface of the cell and may participate in cell-cell interactions.
Proteins can also be anchored in membranes by lipids that are covalently attached to the polypeptide chain (see Chapter 7). Distinct lipid modifications anchor proteins to the cytosolic and extracellular faces of the plasma membrane. Proteins can be anchored to the cytosolic face of the membrane either by the addition of a 14-carbon fatty acid (myristic acid) to their amino terminus or by the addition of either a 16-carbon fatty acid (palmitic acid) or 15- or 20-carbon prenyl groups to the side chains of cysteine residues. Alternatively, proteins are anchored to the extracellular face of the plasma membrane by the addition of glycolipids to their carboxy terminus.
Transport across Cell Membranes
The selective permeability of biological membranes to small molecules allows the cell to control and maintain its internal composition. Only small uncharged molecules can diffuse freely through phospholipid bilayers (). Small nonpolar molecules, such as O2 and CO2, are soluble in the lipid bilayer and therefore can readily cross cell membranes. Small uncharged polar molecules, such as H2O, also can diffuse through membranes, but larger uncharged polar molecules, such as glucose, cannot. Charged molecules, such as ions, are unable to diffuse through a phospholipid bilayer regardless of size; even H+ ions cannot cross a lipid bilayer by free diffusion.
Figure 2.49
Permeability of phospholipid bilayers. Small uncharged molecules can diffuse freely through a phospholipid bilayer. However, the bilayer is impermeable to larger polar molecules (such as glucose and amino acids) and to ions.
Although ions and most polar molecules cannot diffuse across a lipid bilayer, many such molecules (such as glucose) are able to cross cell membranes. These molecules pass across membranes via the action of specific transmembrane proteins, which act as transporters. Such transport proteins determine the selective permeability of cell membranes and thus play a critical role in membrane function. They contain multiple membrane-spanning regions that form a passage through the lipid bilayer, allowing polar or charged molecules to cross the membrane through a protein pore without interacting with the hydrophobic fatty acid chains of the membrane phospholipids.
As discussed in detail in Chapter 12, there are two general classes of membrane transport proteins (). form open pores through the membrane, allowing the free passage of any molecule of the appropriate size. Ion channels, for example, allow the passage of inorganic ions such as Na+, K+, Ca2+, and Cl- across the plasma membrane. Once open, channel proteins form small pores through which ions of the appropriate size and charge can cross the membrane by free diffusion. The pores formed by these channel proteins are not permanently open; rather, they can be selectively opened and closed in response to extracellular signals, allowing the cell to control the movement of ions across the membrane. Such regulated ion channels have been particularly well studied in nerve and muscle cells, where they mediate the transmission of electrochemical signals.
Figure 2.50
Channel and carrier proteins. (A) Channel proteins form open pores through which molecules of the appropriate size (e.g., ions) can cross the membrane. (B) Carrier proteins selectively bind the small molecule to be transported and then undergo a conformational (more...)
In contrast to channel proteins, selectively bind and transport specific small molecules, such as glucose. Rather than forming open channels, carrier proteins act like enzymes to facilitate the passage of specific molecules across membranes. In particular, carrier proteins bind specific molecules and then undergo conformational changes that open channels through which the molecule to be transported can pass across the membrane and be released on the other side.
As described so far, molecules transported by either channel or carrier proteins cross membranes in the energetically favorable direction, as determined by concentration and electrochemical gradients—a process known as . However, carrier proteins also provide a mechanism through which the energy changes associated with transporting molecules across a membrane can be coupled to the use or production of other forms of metabolic energy, just as enzymatic reactions can be coupled to the hydrolysis or synthesis of ATP. For example, molecules can be transported in an energetically unfavorable direction across a membrane (e.g., against a concentration gradient) if their transport in that direction is coupled to ATP hydrolysis as a source of energy—a process called (). The free energy stored as ATP can thus be used to control the internal composition of the cell, as well as to drive the biosynthesis of cell constituents.
Figure 2.51
Model of active transport. Model of active transportEnergy derived from the hydrolysis of ATP is used to transport H+ against the electrochemical gradient (from low to high H+ concentration). Binding of H+ is accompanied by phosphorylation of the carrier (more...)