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Factors determining membrane fluidity
Membrane fluidity can be affected by a number of factors. From physical factors (temperature, pressure, pH, etc.) to biochemical factors (protein/phospholipid ratio, fatty acid saturation levels, cholesterol/phospholipid ratio, etc.), membrane fluidity is a complex parameter that reflects major characteristics of the membrane.

Physical Factors

One way to increase membrane fluidity is to heat up the membrane. Lipids acquire thermal energy when they are heated up; energetic lipids move around more, arranging and rearranging randomly, making the membrane more fluid. At low temperatures, the lipids are laterally ordered and organized in the membrane, and the lipid chains are mostly in the all-trans configuration and pack well together.

The melting temperature $$T_m $$ of a membrane is defined as the temperature across which the membrane transitions from a crystal-like to a fluid-like organization, or viceversa. This phase transition is not an actual state transition, but the two levels of organizations are very similar to a solid and liquid state.


 * $$T < T_m$$: The membrane is in the crystalline phase, the level of order in the bilayer is high and the fluidity is low.
 * $$T > T_m$$: The membrane is in the liquid-crystal phase, the membrane is less ordered and more fluid.

Another way to change membrane fluidity is to change the pressure. In the laboratory, supported lipid bilayers and monolayers can be made artificially. In such cases, one can still speak of membrane fluidity. These membranes are supported by a flat surface, e.g. the bottom of a box. The fluidity of these membranes can be controlled by the lateral pressure applied, e.g. by the side walls of a box.

Biochemical Factors

Unlike physical factors that change the surrounding, membrane composition can also affect its fluidity. The membrane phospholipids incorporate fatty acids of varying length and saturation. Lipids with shorter chains are less stiff and less viscous because they are more susceptible to changes in kinetic energy due to their smaller molecular size and they have less surface area to undergo stabilizing London forces with neighboring hydrophobic chains. Lipid chains with carbon-carbon double bonds (unsaturated) are more rigid than lipids that are saturated with hydrogens, as double bonds cannot freely turn. Because of this rigidity, unsaturated double bonds make it harder for the lipids to pack together by putting kinks into the otherwise straightened hydrocarbon chain. While the individual lipids may be more rigid, membranes made with such lipids are more fluid and have lower melting points: less thermal energy is required to achieve the same level of fluidity as membranes made with lipids with saturated hydrocarbon chains. Incorporation of particular lipids, such as sphingomyelin, into synthetic lipid membranes is known to stiffen a membrane. Such membranes can be described as "a glass state, i.e., rigid but without crystalline order".

Cholesterol belongs to a class of lipids known as sterols. Much like phospholipids, cholesterol shares an amphiphilic nature, but is structurally quite different. It has a polar head hydroxyl group, while the rest of the molecule is hydrophobic, containing a single non-polar hydrocarbon tail and a rigid steroid ring structure. Due to the the presence of this four ring structure, cholesterol is actually a rigid molecule as geometric constraints prevent the bonds within the ring from rotating freely. However, very similarly to phospholipids, cholesterol can insert itself into cell membranes as the hydrophilic hydroxyl head group interacts with the head groups of phospholipids while the rest of the molecule can interact with the hydrophobic fatty acid tails. These interactions influence membrane fluidity, and does so by acting as a bidirectional regulator. At high temperatures, cholesterol's rigid structure stiffens regions of the phospholipid fatty acid chains nearest the polar head groups. Thus leading to this region of the phospholipid bilayer to become less deformable. Conversely, at low temperatures, fluidity is increased as cholesterol intercalates between the phospholipids and prevents them from clustering together and stiffening. The presence of cholesterol also influences the fluidity within the membrane at varying levels increasing more towards the center where the rigid ring is located. These chains act as a "wall" leading to tighter packing of the phospholipids near the surface while the less densely packed regions (center) will allows for more rotation freedom of the acyl chains.

Some drugs, e.g. Losartan, are also known to alter membrane viscosity.