Fluid Mosaic Model

The existence of the plasma membrane was identified in the 1890s, and its chemical components were identified in 1915. The principal components identified at that time were lipids and proteins. The first widely accepted model of the plasma membrane’s structure was proposed in 1935 by Hugh Davson and James Danielli; it was based on the “railroad track” appearance of the plasma membrane in early electron micrographs. They theorized that the structure of the plasma membrane resembles a sandwich, with protein being analogous to the bread, and lipids being analogous to the filling. In the 1950s, advances in microscopy, notably transmission electron microscopy (TEM), allowed researchers to see that the core of the plasma membrane consisted of a double, rather than a single, layer. A new model that better explains both the microscopic observations and the function of that plasma membrane was proposed by S.J. Singer and Garth L. Nicolson in 1972.

The explanation proposed by Singer and Nicolson is called the fluid mosaic model. The model has evolved somewhat over time, but it still best accounts for the structure and functions of the plasma membrane as we now understand them. The fluid mosaic model describes the structure of the plasma membrane as a mosaic of components—including phospholipids, cholesterol, proteins, and carbohydrates—that gives the membrane a fluid character. Plasma membranes range from 5 to 10 nm in thickness. For comparison, human red blood cells, visible via light microscopy, are approximately 8 µm wide, or approximately 1,000 times wider than a plasma membrane. The membrane does look a bit like a sandwich (Figure).

The principal components of a plasma membrane are lipids (phospholipids and cholesterol), proteins, and carbohydrates attached to some of the lipids and some of the proteins. A phospholipid is a molecule consisting of glycerol, two fatty acids, and a phosphate-linked head group. Cholesterol, another lipid composed of four fused carbon rings, is found alongside the phospholipids in the core of the membrane. The proportions of proteins, lipids, and carbohydrates in the plasma membrane vary with cell type, but for a typical human cell, protein accounts for about 50 percent of the composition by mass, lipids (of all types) account for about 40 percent of the composition by mass, with the remaining 10 percent of the composition by mass being carbohydrates. However, the concentration of proteins and lipids varies with different cell membranes. For example, myelin, an outgrowth of the membrane of specialized cells that insulates the axons of the peripheral nerves, contains only 18 percent protein and 76 percent lipid. The mitochondrial inner membrane contains 76 percent protein and only 24 percent lipid. The plasma membrane of human red blood cells is 30 percent lipid. Carbohydrates are present only on the exterior surface of the plasma membrane and are attached to proteins, forming glycoproteins, or attached to lipids, forming glycolipids.

Phospholipids

The main fabric of the membrane is composed of amphiphilic, phospholipid molecules. The hydrophilic or “water-loving” areas of these molecules (which look like a collection of balls in an artist’s rendition of the model) (Figure) are in contact with the aqueous fluid both inside and outside the cell. Hydrophobic, or water-hating molecules, tend to be non-polar. They interact with other non-polar molecules in chemical reactions, but generally do not interact with polar molecules. When placed in water, hydrophobic molecules tend to form a ball or cluster. The hydrophilic regions of the phospholipids tend to form hydrogen bonds with water and other polar molecules on both the exterior and interior of the cell. Thus, the membrane surfaces that face the interior and exterior of the cell are hydrophilic. In contrast, the interior of the cell membrane is hydrophobic and will not interact with water. Therefore, phospholipids form an excellent two-layer cell membrane that separates fluid within the cell from the fluid outside of the cell.

A phospholipid molecule (Figure) consists of a three-carbon glycerol backbone with two fatty acid molecules attached to carbons 1 and 2, and a phosphate-containing group attached to the third carbon. This arrangement gives the overall molecule an area described as its head (the phosphate-containing group), which has a polar character or negative charge, and an area called the tail (the fatty acids), which has no charge. The head can form hydrogen bonds, but the tail cannot. A molecule with this arrangement of a positively or negatively charged area and an uncharged, or non-polar, area is referred to as amphiphilic or “dual-loving.”

This characteristic is vital to the structure of a plasma membrane because, in water, phospholipids tend to become arranged with their hydrophobic tails facing each other and their hydrophilic heads facing out. In this way, they form a lipid bilayer—a barrier composed of a double layer of phospholipids that separates the water and other materials on one side of the barrier from the water and other materials on the other side. In fact, phospholipids heated in an aqueous solution tend to spontaneously form small spheres or droplets (called micelles or liposomes), with their hydrophilic heads forming the exterior and their hydrophobic tails on the inside (Figure).

Proteins

Proteins make up the second major component of plasma membranes. Integral proteins (some specialized types are called integrins) are, as their name suggests, integrated completely into the membrane structure, and their hydrophobic membrane-spanning regions interact with the hydrophobic region of the the phospholipid bilayer (Figure). Single-pass integral membrane proteins usually have a hydrophobic transmembrane segment that consists of 20–25 amino acids. Some span only part of the membrane—associating with a single layer—while others stretch from one side of the membrane to the other, and are exposed on either side. Some complex proteins are composed of up to 12 segments of a single protein, which are extensively folded and embedded in the membrane (Figure). This type of protein has a hydrophilic region or regions, and one or several mildly hydrophobic regions. This arrangement of regions of the protein tends to orient the protein alongside the phospholipids, with the hydrophobic region of the protein adjacent to the tails of the phospholipids and the hydrophilic region or regions of the protein protruding from the membrane and in contact with the cytosol or extracellular fluid.

Peripheral proteins are found on the exterior and interior surfaces of membranes, attached either to integral proteins or to phospholipids. Peripheral proteins, along with integral proteins, may serve as enzymes, as structural attachments for the fibers of the cytoskeleton, or as part of the cell’s recognition sites. These are sometimes referred to as “cell-specific” proteins. The body recognizes its own proteins and attacks foreign proteins associated with invasive pathogens.

Carbohydrates

Carbohydrates are the third major component of plasma membranes. They are always found on the exterior surface of cells and are bound either to proteins (forming glycoproteins) or to lipids (forming glycolipids) (Figure). These carbohydrate chains may consist of 2–60 monosaccharide units and can be either straight or branched. Along with peripheral proteins, carbohydrates form specialized sites on the cell surface that allow cells to recognize each other. These sites have unique patterns that allow the cell to be recognized, much the way that the facial features unique to each person allow him or her to be recognized. This recognition function is very important to cells, as it allows the immune system to differentiate between body cells (called “self”) and foreign cells or tissues (called “non-self”). Similar types of glycoproteins and glycolipids are found on the surfaces of viruses and may change frequently, preventing immune cells from recognizing and attacking them.

These carbohydrates on the exterior surface of the cell—the carbohydrate components of both glycoproteins and glycolipids—are collectively referred to as the glycocalyx (meaning “sugar coating”). The glycocalyx is highly hydrophilic and attracts large amounts of water to the surface of the cell. This aids in the interaction of the cell with its watery environment and in the cell’s ability to obtain substances dissolved in the water. As discussed above, the glycocalyx is also important for cell identification, self/non-self determination, and embryonic development, and is used in cell-cell attachments to form tissues.

EVOLUTION CONNECTION

How Viruses Infect Specific OrgansGlycoprotein and glycolipid patterns on the surfaces of cells give many viruses an opportunity for infection. HIV and hepatitis viruses infect only specific organs or cells in the human body. HIV is able to penetrate the plasma membranes of a subtype of lymphocytes called T-helper cells, as well as some monocytes and central nervous system cells. The hepatitis virus attacks liver cells.

These viruses are able to invade these cells, because the cells have binding sites on their surfaces that are specific to and compatible with certain viruses (Figure). Other recognition sites on the virus’s surface interact with the human immune system, prompting the body to produce antibodies. Antibodies are made in response to the antigens or proteins associated with invasive pathogens, or in response to foreign cells, such as might occur with an organ transplant. These same sites serve as places for antibodies to attach and either destroy or inhibit the activity of the virus. Unfortunately, these recognition sites on HIV change at a rapid rate because of mutations, making the production of an effective vaccine against the virus very difficult, as the virus evolves and adapts. A person infected with HIV will quickly develop different populations, or variants, of the virus that are distinguished by differences in these recognition sites. This rapid change of surface markers decreases the effectiveness of the person’s immune system in attacking the virus, because the antibodies will not recognize the new variations of the surface patterns. In the case of HIV, the problem is compounded by the fact that the virus specifically infects and destroys cells involved in the immune response, further incapacitating the host.

Membrane Fluidity

The mosaic characteristic of the membrane, described in the fluid mosaic model, helps to illustrate its nature. The integral proteins and lipids exist in the membrane as separate but loosely attached molecules. These resemble the separate, multicolored tiles of a mosaic picture, and they float, moving somewhat with respect to one another. The membrane is not like a balloon, however, that can expand and contract; rather, it is fairly rigid and can burst if penetrated or if a cell takes in too much water. However, because of its mosaic nature, a very fine needle can easily penetrate a plasma membrane without causing it to burst, and the membrane will flow and self-seal when the needle is extracted.

The mosaic characteristics of the membrane explain some but not all of its fluidity. There are two other factors that help maintain this fluid characteristic. One factor is the nature of the phospholipids themselves. In their saturated form, the fatty acids in phospholipid tails are saturated with bound hydrogen atoms. There are no double bonds between adjacent carbon atoms. This results in tails that are relatively straight. In contrast, unsaturated fatty acids do not contain a maximal number of hydrogen atoms, but they do contain some double bonds between adjacent carbon atoms; a double bond results in a bend in the string of carbons of approximately 30 degrees (Figure).

Thus, if saturated fatty acids, with their straight tails, are compressed by decreasing temperatures, they press in on each other, making a dense and fairly rigid membrane. If unsaturated fatty acids are compressed, the “kinks” in their tails elbow adjacent phospholipid molecules away, maintaining some space between the phospholipid molecules. This “elbow room” helps to maintain fluidity in the membrane at temperatures at which membranes with saturated fatty acid tails in their phospholipids would “freeze” or solidify. The relative fluidity of the membrane is particularly important in a cold environment. A cold environment tends to compress membranes composed largely of saturated fatty acids, making them less fluid and more susceptible to rupturing. Many organisms (fish are one example) are capable of adapting to cold environments by changing the proportion of unsaturated fatty acids in their membranes in response to the lowering of the temperature.

LINK TO LEARNING

Visit this site to see animations of the fluidity and mosaic quality of membranes.

Animals have an additional membrane constituent that assists in maintaining fluidity. Cholesterol, which lies alongside the phospholipids in the membrane, tends to dampen the effects of temperature on the membrane. Thus, this lipid functions as a buffer, preventing lower temperatures from inhibiting fluidity and preventing increased temperatures from increasing fluidity too much. Thus, cholesterol extends, in both directions, the range of temperature in which the membrane is appropriately fluid and consequently functional. Cholesterol also serves other functions, such as organizing clusters of transmembrane proteins into lipid rafts.