One property of a

lipid bilayer The lipid bilayer (or phospholipid bilayer) is a thin polar membrane made of two layers of lipid molecules. These membranes are flat sheets that form a continuous barrier around all cells. The cell membranes of almost all organisms and many vir ...

is the relative mobility (fluidity) of the individual lipid molecules and how this mobility changes with temperature. This response is known as the phase behavior of the bilayer. Broadly, at a given temperature a lipid bilayer can exist in either a liquid or a solid phase. The solid phase is commonly referred to as a “gel” phase. All lipids have a characteristic temperature at which they undergo a transition ( melt) from the gel to liquid phase. In both phases the lipid molecules are constrained to the two dimensional plane of the membrane, but in liquid phase bilayers the molecules

diffuse Diffusion is the net movement of anything (for example, atoms, ions, molecules, energy) generally from a region of higher concentration to a region of lower concentration. Diffusion is driven by a gradient in Gibbs free energy or chemical p ...

freely within this plane. Thus, in a liquid bilayer a given lipid will rapidly exchange locations with its neighbor millions of times a second and will, through the process of a

random walk In mathematics, a random walk is a random process that describes a path that consists of a succession of random steps on some mathematical space. An elementary example of a random walk is the random walk on the integer number line \mathbb Z ...

, migrate over long distances.H. C. Berg, "Random Walks in Biology". Extended Paperback Ed. ed. 1993, Princeton, NJ: Princeton University Press.

Motion constraints

In contrast to this large in-plane mobility, it is very difficult for lipid molecules to flip-flop from one side of the

to the other. In a phosphatidylcholine-based bilayer this process typically occurs over a timescale of weeks.R. Homan and H. J. Pownall."Transbilayer diffusion of phospholipids: dependence on headgroup structure and acyl chain length." Biochimica et Biophysica Acta 938. (1988) 155 -166. This discrepancy can be understood in terms of the basic structure of the bilayer. For a lipid to flip from one leaflet to the other, its hydrated headgroup must cross the

hydrophobic In chemistry, hydrophobicity is the physical property of a molecule that is seemingly repelled from a mass of water (known as a hydrophobe). In contrast, hydrophiles are attracted to water. Hydrophobic molecules tend to be nonpolar and, ...

core of the bilayer, an energetically unfavorable process. Unlike liquid phase bilayers, the lipids in a gel phase bilayer are locked in place and exhibit neither flip-flop nor lateral mobility. Due to this limited mobility, gel bilayers lack an important property of liquid bilayers: the ability to reseal small holes. Liquid phase bilayers can spontaneously heal small voids, much the same way a film of oil on water could flow in to fill a gap. This functionality is one of the reasons that

cell membranes The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of all cells from the outside environment (t ...

are usually composed of fluid phase bilayers. Motion constraints on lipids in lipid bilayers are also imposed by presence of proteins in biological membranes, especially so in the

annular lipid shell Annular lipids (also called shell lipids or boundary lipids) are a set of lipids or lipidic molecules which preferentially bind or stick to the surface of membrane proteins in biological cells. They constitute a layer, or an annulus/ shell, of lipid ...

'attached' to surface of integral membrane proteins.

Physical origins

The phase behavior of lipid bilayers is largely determined by the strength of the attractive Van der Waals interactions between adjacent lipid molecules. The extent of this interaction is in turn governed by how long the

lipid Lipids are a broad group of naturally-occurring molecules which includes fats, waxes, sterols, fat-soluble vitamins (such as vitamins A, D, E and K), monoglycerides, diglycerides, phospholipids, and others. The functions of lipids in ...

tails are and how well they can pack together. Longer tailed lipids have more area over which to interact, increasing the strength of this interaction and consequently decreasing the lipid mobility. Thus, at a given temperature, a short-tailed lipid will be more fluid than an otherwise identical long-tailed lipid.W. Rawicz, K. C. Olbrich, T. McIntosh, D. Needham and E. Evans."Effect of chain length and unsaturation on elasticity of lipid bilayers." Biophysical Journal. 79. (2000) 328-39. Another way of expressing this would be to say that the gel to liquid phase transition temperature increases with increasing number of carbons in the lipid

alkane In organic chemistry, an alkane, or paraffin (a historical trivial name that also has other meanings), is an acyclic saturated hydrocarbon. In other words, an alkane consists of hydrogen and carbon atoms arranged in a tree structure in wh ...

chains. Saturated phosphatidylcholine lipids with tails longer than 14 carbons are solid at room temperature, while those with fewer than 14 are liquid. This phenomenon is analogous to the fact that

paraffin wax Paraffin wax (or petroleum wax) is a soft colorless solid derived from petroleum, coal, or oil shale that consists of a mixture of hydrocarbon molecules containing between 20 and 40 carbon atoms. It is solid at room temperature and begins t ...

, which is composed of long alkanes, is solid at room temperature, while octane (

gasoline Gasoline (; ) or petrol (; ) (see ) is a transparent, petroleum-derived flammable liquid that is used primarily as a fuel in most spark-ignited internal combustion engines (also known as petrol engines). It consists mostly of organic c ...

), a short alkane, is liquid. Aside from chain length, transition temperature can also be affected by the degree of unsaturation of the lipid tails. An unsaturated

double bond In chemistry, a double bond is a covalent bond between two atoms involving four bonding electrons as opposed to two in a single bond. Double bonds occur most commonly between two carbon atoms, for example in alkenes. Many double bonds exist betwee ...

can produce a kink in the alkane chain, disrupting the regular periodic structure. This disruption creates extra free space within the bilayer which allows additional flexibility in the adjacent chains. It is this disruption of packing that leads to lower transition temperatures with increasing double bonds. This is a particularly powerful effect; decreasing the overall chain length by one carbon usually alters the transition temperature of a lipid by ten degrees Celsius or less, but adding a single double bond can decrease the transition temperature by fifty degrees or more (see table). An example of this effect can be noted in everyday life as

butter Butter is a dairy product made from the fat and protein components of churned cream. It is a semi-solid emulsion at room temperature, consisting of approximately 80% butterfat. It is used at room temperature as a spread, melted as a condim ...

, which has a large percentage

saturated fats A saturated fat is a type of fat in which the fatty acid chains have all single bonds. A fat known as a glyceride is made of two kinds of smaller molecules: a short glycerol backbone and fatty acids that each contain a long linear or branched c ...

, is solid at room temperature while

vegetable oil Vegetable oils, or vegetable fats, are oils extracted from seeds or from other parts of fruits. Like animal fats, vegetable fats are ''mixtures'' of triglycerides. Soybean oil, grape seed oil, and cocoa butter are examples of seed oils, or f ...

, which is mostly unsaturated, is liquid.

Mixed systems

Bilayers need not be composed of a single type of lipid and, in fact, most natural membranes are a complex mixture of different lipid molecules. Such mixtures often exhibit properties intermediate to their components, but are also capable of a phenomenon not seen in single component systems:

phase separation Phase separation is the creation of two distinct phases from a single homogeneous mixture. The most common type of phase separation is between two immiscible liquids, such as oil and water. Colloids are formed by phase separation, though no ...

. If some of the components are liquid at a given temperature while others are in the gel phase, the two phases can coexist in spatially separated populations. This phase separation plays a critical role in biochemical phenomena because membrane components such as

proteins Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...

can partition into one or the other phase and thus be locally concentrated or activated.

Cholesterol

The presence of

cholesterol Cholesterol is any of a class of certain organic molecules called lipids. It is a sterol (or modified steroid), a type of lipid. Cholesterol is biosynthesized by all animal cells and is an essential structural component of animal cell memb ...

exerts a profound but complicated influence on lipid bilayer properties because of its unique physical characteristics. Although it is a lipid, cholesterol bears little resemblance to a

phospholipid Phospholipids, are a class of lipids whose molecule has a hydrophilic "head" containing a phosphate group and two hydrophobic "tails" derived from fatty acids, joined by an alcohol residue (usually a glycerol molecule). Marine phospholipids typ ...

. The

hydrophilic A hydrophile is a molecule or other molecular entity that is attracted to water molecules and tends to be dissolved by water.Liddell, H.G. & Scott, R. (1940). ''A Greek-English Lexicon'' Oxford: Clarendon Press. In contrast, hydrophobes are n ...

domain of cholesterol is quite small, consisting of a single

hydroxyl In chemistry, a hydroxy or hydroxyl group is a functional group with the chemical formula and composed of one oxygen atom covalently bonded to one hydrogen atom. In organic chemistry, alcohols and carboxylic acids contain one or more hydrox ...

group. Adjacent to this hydroxyl group is a rigid planar structure composed of several fused rings. At the opposite end of the ring structure is a short single chain tail. It has been known for decades that the addition of cholesterol to a fluid phase bilayer decreases its permeability to water. The mode of this interaction has more recently been shown to be due to cholesterol intercalating between lipid molecules, filling in free space and decreasing the flexibility of surrounding lipid chains. This interaction also increases the mechanical rigidity of fluid membrane lipid bilayersD. Boal, "Mechanics of the Cell". 2002, Cambridge, UK: Cambridge University Press and decreases their lateral diffusion coefficient. In contrast, the addition of cholesterol to gel phase bilayers disrupts local packing order, increasing the diffusion coefficient and decreasing the elastic modulus. Interactions of cholesterol with multi-component systems are even more complicated, as these can result in intricate

phase diagram A phase diagram in physical chemistry, engineering, mineralogy, and materials science is a type of chart used to show conditions (pressure, temperature, volume, etc.) at which thermodynamically distinct phases (such as solid, liquid or gaseous ...

s. One lipid-cholesterol system that has recently been studied intently is the lipid raft. Lipid rafts are cholesterol-enriched gel domains that have been potentially implicated in certain cell signaling processes, but the subject remains controversial, with some researchers doubting even their existence in vivo.

Lipid polymorphism

Mixed lipid liposomes can undergo changes into different phase dispersion structures, called lipid polymorphisms, for example, spherical

micelles A micelle () or micella () (plural micelles or micellae, respectively) is an aggregate (or supramolecular assembly) of surfactant amphipathic lipid molecules dispersed in a liquid, forming a colloidal suspension (also known as associated coll ...

lamellae and hexagonal phase cylinders, depending on physical and chemical changes in their microenvironment.

Phase transition In chemistry, thermodynamics, and other related fields, a phase transition (or phase change) is the physical process of transition between one state of a medium and another. Commonly the term is used to refer to changes among the basic states ...

temperature of liposomes and biological membranes can be measured using

calorimetry In chemistry and thermodynamics, calorimetry () is the science or act of measuring changes in ''state variables'' of a body for the purpose of deriving the heat transfer associated with changes of its state due, for example, to chemical re ...

magnetic resonance spectroscopy Nuclear magnetic resonance spectroscopy, most commonly known as NMR spectroscopy or magnetic resonance spectroscopy (MRS), is a spectroscopic technique to observe local magnetic fields around atomic nuclei. The sample is placed in a magnetic fie ...

and other techniques.

References