Marcus Long

Brandeis University

John, IL, US

I have heard conflicting answers to the following question and wonder which is correct: If unesterified cholesterol were added into the bilayer membrane of human cells in increasing amounts, would the cell membranes become more stiff or less?

Marcus Long
HHMI predoctoral fellow,
Chemistry Department,
Brandeis University
Cholesterol is a rigid polycyclic compound (i.e, a steroid) that is mostly apolar and can insert into the lipid tails of membrane phospholipids (which are oriented perpendicularly to the membrane surface). Cholesterol has one hydroxyl group, which is believed to interact with the polar phosphate heads of the phospholipids.

In a membrane, cholesterol acts as an “impurity.” Thus, membranes with high cholesterol are less subject to phase transition that can lead to crystallization (i.e., going from fluid to solid). Think of when salt or antifreeze is added to water; it increases the range of temperatures over which water is “water” and not ice.

However, because of its rigid structure and because it interacts with phosphate heads, cholesterol has the effect of producing order in the membrane lipids around it. These characteristics are consistent with the observation that the higher the cholesterol content in a membrane, the lower the membrane’s fluidity, and vice versa.

Because of these two somewhat opposing effects (increased fluid range, but decreased fluidity), the role of cholesterol in membranes can seem confusing. Ultimately, however, cholesterol behaves just as any other impurity: It broadens the range over which the membrane is a liquid but increases the order of the membrane.

Although membrane fluidity in mammals (which are warm-blooded) is typically regulated with cholesterol, in Escherichia coli (which grow at almost any temperature, although 37°C is optimal) membrane fluidity is regulated at different growth temperatures by changing the unsaturation of fatty acids in the membrane. For instance, long-chain unsaturated fatty acid–derived phospholipids have low melting temperatures; as the unsaturation of the acids increases, the melting temperature lowers. Thus, as the growth temperature of E. coli is lowered, the degree of unsaturation in the lipids in the membrane increases. A similar effect is found in cold-adapted fish (which are also cold-blooded).

07/20/12 13:21