Question

Compare and contrast the influence of different phospholipid chain lengths and degree of saturation in membrane lipids on membrane fluidity.

Answer 1

The phospholipid bilayer is the main fabric of the membrane. The bilayer's structure causes the membrane to be semipermeable. The hydrophobic core blocks the diffusion of hydrophilic ions and polar molecules. Small hydrophobic molecules and gases, which can dissolve in the membrane's core, cross it with ease. Other molecules require proteins to transport them across the membrane.

The fluidity of the membrane is regulated by the types of phospholipids and the presence of cholesterol. Second, the phospholipid membrane is selectively permeable.

The cell membrane is dynamic in that the individual phospholipids and proteins that constitute the membrane are moving rapidly within the membrane. Thermal energy causes lipids and proteins to diffuse within membranes. Scientists have measured the rate at which lipids and proteins diffuse and one estimate is that a lipid can circumnavigate a bacterial membrane in one second.

The diffusive nature of membranes has important biological and medical consequences. Without any other system acting on a membrane, the lipids and proteins in the membrane will be randomly distributed throughout that membrane. As we will see, cells expend a considerable amount of energy to create domains with in membranes that contain a specific set of proteins and sometimes lipids. These domains play important roles in cell adhesion and communication.

phospholipids have a polar head group and two hydrophobic hydrocarbon tails. The tails are usually fatty acids, and they can differ in length (they normally contain between 14 and 24 carbon atoms). One tail usually has one or more cis-double bonds (i.e., it is unsaturated), while the other tail does not (i.e., it is saturated). Each double bond creates a small kink in the tail. Differences in the length and saturation of the fatty acid tails are important because they influence the ability of phospholipidmolecules to pack against one another, thereby affecting the fluidity of the membrane.

It is the shape and amphipathic nature of the lipid molecules that cause them to form bilayers spontaneously in aqueous environments. Hydrophilic molecules dissolve readily in water because they contain charged groups or uncharged polar groups that can form either favorable electrostatic interactions or hydrogen bonds with water molecules. Hydrophobic molecules, by contrast, are insoluble in water because all, or almost all, of their atoms are uncharged and nonpolar and therefore cannot form energetically favorable interactions with water molecules. If dispersed in water, they force the adjacent water molecules to reorganize into icelike cages that surround the hydrophobic molecule. Because these cage structures are more ordered than the surrounding water, their formation increases the free energy. This free energy cost is minimized, however, if the hydrophobic molecules (or the hydrophobic portions of amphipathic molecules) cluster together so that the smallest number of water molecules is affected.

For the above reason, lipid molecules spontaneously aggregate to bury their hydrophobic tails in the interior and expose their hydrophilic heads to water. Depending on their shape, they can do this in either of two ways: they can form spherical micelles, with the tails inward, or they can form bimolecular sheets, or bilayers, with the hydrophobic tails sandwiched between the hydrophilic head groups.

Being cylindrical, phospholipid molecules spontaneously form bilayers in aqueous environments. In this energetically most-favorable arrangement, the hydrophilic heads face the water at each surface of the bilayer, and the hydrophobic tails are shielded from the water in the interior. The same forces that drive phospholipids to form bilayers also provide a self-healing property. A small tear in the bilayer creates a free edge with water; because this is energetically unfavorable, the lipids spontaneously rearrange to eliminate the free edge. (In eucaryotic plasma membranes, larger tears are repaired by the fusion of intracellular vesicles.) The prohibition against free edges has a profound consequence: the only way for a bilayer to avoid having edges is by closing in on itself and forming a sealed compartment. This remarkable behavior, fundamental to the creation of a living cell, follows directly from the shape and amphipathic nature of the phospholipid molecule.

Various techniques have been used to measure the motion of individual lipid molecules and their different parts. One can construct a lipid molecule, for example, whose polar head group carries a “spin label,” such as a nitroxyl group (>N-O); this contains an unpaired electron whose spin creates a paramagnetic signal that can be detected by electron spin resonance (ESR) spectroscopy. The motion and orientation of a spin-labeled lipid in a bilayer can be deduced from the ESR spectrum. Such studies show that phospholipid molecules in synthetic bilayers very rarely migrate from the monolayer (also called a leaflet) on one side to that on the other. This process, known as “flip-flop,” occurs less than once a month for any individual molecule. In contrast, lipid molecules readily exchange places with their neighbors within a monolayer (~107 times per second). This gives rise to a rapid lateral diffusion, with a diffusion coefficient (D) of about 10-8 cm2/sec, which means that an average lipid molecule diffuses the length of a large bacterial cell (~2 ?m) in about 1 second. These studies have also shown that individual lipid molecules rotate very rapidly about their long axis and that their hydrocarbon chains are flexible.

The Fluidity of a Lipid Bilayer Depends on Its Composition

The fluidity of cell membranes has to be precisely regulated. Certain membrane transport processes and enzymeactivities, for example, cease when the bilayer viscosity is experimentally increased beyond a threshold level. The fluidity of a lipid bilayer depends on both its composition and its temperature, as is readily demonstrated in studies of synthetic bilayers. A synthetic bilayer made from a single type of phospholipid changes from a liquid state to a two-dimensional rigid crystalline (or gel) state at a characteristic freezing point. This change of state is called a phase transition, and the temperature at which it occurs is lower (that is, the membrane becomes more difficult to freeze) if the hydrocarbon chains are short or have double bonds. A shorter chain length reduces the tendency of the hydrocarbon tails to interact with one another, and cis-double bonds produce kinks in the hydrocarbon chains that make them more difficult to pack together, so that the membrane remains fluid at lower temperatures. Bacteria, yeasts, and other organisms whose temperature fluctuates with that of their environment adjust the fatty acidcomposition of their membrane lipids to maintain a relatively constant fluidity. As the temperature falls, for instance, fatty acids with more cis-double bonds are synthesized, so the decrease in bilayer fluidity that would otherwise result from the drop in temperature is avoided.

The lipid bilayer of many cell membranes is not composed exclusively of phospholipids, however; it often also contains cholesterol and glycolipids. Eucaryotic plasma membranes contain especially large amounts of cholesterol—up to one molecule for every phospholipid molecule. The cholesterol molecules enhance the permeability-barrier properties of the lipid bilayer. They orient themselves in the bilayer with their hydroxyl groups close to the polar head groups of the phospholipid molecules. In this position, their rigid, platelike steroid rings interact with—and partly immobilize—those regions of the hydrocarbon chains closest to the polar head groups . By decreasing the mobility of the first few CH2 groups of the hydrocarbon chains of the phospholipid molecules, cholesterol makes the lipid bilayer less deformable in this region and thereby decreases the permeability of the bilayer to small water-soluble molecules. Although cholesterol tends to make lipid bilayers less fluid, at the high concentrations found in most eucaryotic plasma membranes, it also prevents the hydrocarbon chains from coming together and crystallizing. In this way, it inhibits possible phase transitions.