Hydrophobic Effect

Because water is so good at forming hydrogen bonds with itself, it is most hospitable to molecules or ions that least disrupt its H‐bonding network. Watching oils float on the surface of water demonstrates that oil molecules are nonpolar — they don't carry a charge or polarity, and do not dissolve in water. When an oil or other nonpolar compound encounters water, the compound disrupts the H‐bonding network of water and forces it to re‐form around the nonpolar molecule, making a cage of sorts around the nonpolar molecule. This cage is an ordered structure, and so is unfavored by the Second Law of Thermodynamics, which states that spontaneous reactions proceed with an increase in entropy (disorder).

How to resolve this dilemma? If the nonpolar molecules come together, then fewer water molecules are required to form a cage around them. As an analogy, consider the ordered water structure to be like paint around a cubic block. If you have four blocks to paint, and each block is 1 cm along each side, each block would require 6 cm 2 worth of paint if you paint them separately. However, if you put the four blocks together in a square pattern, you don't need to paint the inside surfaces of the cubes. A total of only 16 cm 2 rather than 24 cm 2 surface needs to be painted as Figure 1 shows.


                           Figure 1

The tendency of nonpolar molecules to self‐associate in water rather than to dissolve individually is called the hydrophobic effect. The term is somewhat misleading because it refers to the molecules themselves, where in reality it is due to the H‐bonding nature of water, but it is used almost universally, and biochemists often speak of the hydrophobic side chains of a molecule as a shorthand for the complexities of discussing water structure as it is affected by nonpolar constituents of biomolecules.

Many biomolecules are amphipathic, that is, they have both hydrophobic (water‐hating) and hydrophilic (water‐loving) parts. For example, palmitic acid has a carboxylic acid functional group attached to a long hydrocarbon tail. When its sodium salt, sodium palmitate, is dissolved in water, the hydrocarbon tails associate due to the hydrophobic effect, leaving the carboxylate groups to associate with water. The fatty acid salt forms a micelle — a spherical droplet arranged with the hydrocarbon chains inside and the carboxylate groups inside on the outside of the droplet. Sodium palmitate is a major constituent of soap. Fats are triglyceride esters, composed of three fatty acids esterified to a single glycerol molecules. An ester linkage is a covalent bond between a carboxylic acid and an alcohol. Soap micelles mobilize fats and other hydrophobic substances by dissolving them in the interior of the micelle. Because the micelles are suspended in water, the fat is mobilized from the surface of the object being cleaned. Detergents are stronger cleaning agents than are soaps, mostly because their hydrophilic component is more highly charged than the fatty acid component of a soap. For example, sodium dodecyl sulfate is a component of commercially available hair shampoos. It is a powerful enough detergent that it is often used experimentally to disrupt the hydrophobic interactions that hold membranes together or that contribute to protein shape.

Membrane associations

Glycerol esters of fatty acids are a large component of biological membranes. These molecules differ from those found in fats in that they contain only two fatty acid side chains and a third, hydrophilic component, making them amphipathic. Amphipathic molecules contain both polar (having a dipole) and nonpolar parts. For example, phosphatidylcholine, a common component of membranes, contains two fatty acids (the hydrophobic portion) and a phosphate ester of choline, itself a charged compound: 

When phosphatidylcholine is suspended in water, the molecules associate by the hydrophobic effect, with the charged portion facing the solvent and the fatty acid side chains associating with each other. Instead of making a micelle, however, as palmitate does, these molecules associate into a bilayer, which eventually forms a spherical vesicle (termed a liposome) with a defined inside and outside. Liposomes are clearly similar to cell membranes, although they differ in some respects.

Biological membranes are bilayers and contain several types of lipids; some more often associated with the outside face of the cell, and others face the inside. Biological membranes also contain a large number of protein components. Membranes are semipermeable, naturally excluding hydrophilic compounds (carbohydrates, proteins, and ions, for example) while allowing oxygen, proteins, and water to pass freely.