Water forms a highly ordered network of intermolecular hydrogen bonds. It is the strength of all the hydrogen bonds combined that imparts the liquid properties to water. Polar or hydrophilic substances dissolve in water because they form hydrogen bonds and electrostatic interactions with water molecules.

Non-polar or hydrophobic substances, on the other hand, are unable to form such interactions, and consequently, are immiscible with water. Addition of no polar substances to water disrupts intermolecular hydrogen bonding of water molecules and creates a cavity which is devoid of the water molecules.

At the suface of the cavity, water molecules rearrange in an orderly manner This results in a thermodynamically unfavorable decrease in entropy. To compensate for the loss of entropy, water molecules force the hydrophobicmolecules to cluster and thus occupy the minimum space. This phenomenon is known as the hydrophobic effect and the “forces” between hydrophobic regionsare called hydrophobic interactions.

Hydrophobic interactions play a major role in defining the native tertiary structure of proteins. Proteins consist of polar and non-polar amino acids. In water-soluble proteins, hydrophobic domains rich in non-polar amino acids are folded in together and thus are shielded from the aqueous environment. In membrane proteins, some hydrophobic regions that otherwise would be exposed
to the aqueous environment are surrounded by lipids.