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. ([link])

The principal components of a plasma membrane are lipids (phospholipids and cholesterol), proteins, and carbohydrates. The proportions of proteins, lipids, and carbohydrates in the plasma membrane vary with organism and 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, 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. Amphiphilic molecules such as phospholipids consist of hydrophilic or “water-loving” areas and hydrophobic, or "water-hating" areas. On a phospholipid, the three-carbon glycerol backbone attached to a phosphate-containing group (review module 3.1) composes the 'head' group of a phospholipid. The 'tail' group consists of fatty acid chains which can be either saturated or unsaturated.

The amphiphilic nature of the phospholipid is vital to the structure of a plasma membrane. In water, phospholipids spontaneously arrange themselves 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.

Possible Discussion

In your own words, explain why phospholipids tend to spontaneously orient themselves into something resembling a membrane when placed in water.

Possible Discussion

The fact that phospholipids spontaneously form bilayers and other similar structures is a huge advantage for cells. Why? What would the effects be on the cell if this process was not spontaneous?

Possible discussion

Note that the phospholipid depicted above has an R group linked to the phosphate group. Recall that this designation is generic - these can be different than the R groups on amino acids. What might be a benefit/purpose of "functionalizing" or "decorating" different lipids with different R groups? Think of the functional requirements for membranes stipulated above.

Membrane 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 ([link]). 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 ([link]). 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 either the exterior or interior surfaces of membranes; and weakly or temporarily associated with the membranes. They can be attached (interact with) either to integral membrane proteins or simply interact weakly with the phospholipids within the membrane.

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 molecules and they 'float' in the membrane, 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.

Possible Discussion

Organisms can be found living in extreme temperature conditions. Both in extreme cold or extreme heat. What types of differences would you expect to see in the lipid composition of organisms that live at these extremes?

Saturated fatty acids, with straight tails, are compressed by decreasing temperatures, and they will press in on each other, making a dense and fairly rigid membrane. When unsaturated fatty acids are compressed, the “kinked” 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 high concentrations of saturated fatty acid tails 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.

Cholesterol

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.

Review of the Components of the Membrane

The Components and Functions of the Plasma Membrane
Component	Location
Phospholipid	Main fabric of the membrane
Cholesterol	Between phospholipids and between the two phospholipid layers of animal cells
Integral proteins (for example, integrins)	Embedded within the phospholipid layer(s). May or may not penetrate through both layers
Peripheral proteins	On the inner or outer surface of the phospholipid bilayer; not embedded within the phospholipids
Carbohydrates (components of glycoproteins and glycolipids)	Generally attached to proteins on the outside membrane layer

Why is it advantageous for the cell membrane to be fluid in nature?

The fluid characteristic of the cell membrane allows greater flexibility to the cell than it would if the membrane were rigid. It also allows the motion of membrane components, required for some types of membrane transport.

Selective Permeability

Selective permeability of the cell membrane refers to its ability to differentiate between different types of molecules, only allowing some molecules through while blocking others. Some of this selective property stems from the intrinsic diffusion rates for different molecules across a membrane. A second factor affecting the relative rates of movement of various substances across a biological membrane is activity of various protein-based membrane transporters, both passive and active, that will be discussed in more detail in subsequent sections. First we take on the notion of intrinsic rates of diffusion across the membrane.

Relative PermeabilitiesThe fact that different substances might cross a biological membrane at different rates should be relatively intuitive. There are differences in the mosaic composition of membranes in biology and differences in the sizes, flexibility and chemical properties of molecules so it stands to reason that the permeability rates vary. It is a complicated landscape. The permeability of a substance across a biological membrane can be measured experimentally and the rate of movement across a membrane reported in what are known as membrane permeability coefficients.

Membrane Permeablility CoefficientsBelow in Figure 7, a variety of compounds are plotted with respect to their membrane permeability coefficients (MPC) as measured against simple biochemical approximation of a real biological membrane. The reported permeability coefficient for this system is the rate at which simple diffusion through a membrane occurs and is reported in units of centimeters per second (cm/s). The permeability coefficient is proportional to the partition coefficient and is inversely proportional to the membrane thickness.

It is important that you are able to read and interpret the diagram below. The larger the coefficient, the more permeable the membrane is to the solute. For example, hexanoic acid is very permeable, a MPC of 0.9; acetic acid, water and ethanol have MPC between 0.01 and 0.001 (see the figure 5), they are less permeable than hexanoic acid. Where as ions, such as sodium (Na⁺) have an MPC of 10^-12, and cross the membrane at a comparatively slow rate.

While there are certain trends or chemical properties that can be roughly associated with different compound permeability (small thing go through "fast", big things "slowly", charged things not at all etc.) we caution against over-generalizing. The molecular determinants of membrane permeability are complicated and involve numerous factors including the specific composition of the membrane, temperature, ionic composition, hydration, the chemical properties of the solute, the potential chemical interactions between the solute in solution and in the membrane, the dielectric properties of materials, and the energy trade-offs associated with moving substances into and out of various environments. So, in this class, rather than try to apply "rules" we will strive to develop a general sense of some properties that can influence permeability and leave the assignment of absolute permeability to experimentally reported rates. In addition, we will also try to minimize the use of vocabulary that depends on a frame of reference. For instance, saying that compound A diffuses "quickly" or "slowly" across a bilayer only means something if the terms "quickly" or "slowly" are numerically defined or the biological context understood. More on that in the following section.