The solubility of proteins in aqueous media is widely variable, from
virtually zero to about 35%by volume. Both protein composition and
conformation, and the environment, i.e., solvent composition and tempera-
ture, cause the variation. There is no good quantitative theory based on first
principles: proteins are too intricate. Nevertheless, some general rules can be
given and the effect of some environmental variables can be predicted
semiquantitatively.
The solubility of a globular protein is closely related to itssurface
properties, i.e., on the groups that are in contact with the solvent. The free
energy involved is primarily due to hydrophobic and electrostatic
interactions. The greater the proportion of apolar groups on the surface
of a protein, the poorer its solubility in water, whereas a larger proportion
of charged groups enhances solubility. It may thus be useful broadly to
classify proteins as hydrophobic or hydrophilic, meaning the surface
properties. As was already mentioned, a fairly large surface hydrophobicity
often leads to the association of polypeptide chains into a specific
quaternary structure. These oligomeric proteins then may have good
solubility, since many apolar groups have been shielded from the solvent (as
illustrated in Figure 7.3d).
Size. The larger the protein molecules, the smaller the decrease in
molar translational entropy upon precipitation. Hence the larger the
decrease in free energy and the smaller their solubility. This especially
applies toglobularproteins, which have a relatively small conformational
entropy. Disordered proteins behave somewhat differently at a
concentration above the solubility: they tend to form a ‘‘coacervate,’’ i.e.,
a highly concentrated aqueous phase, rather than a precipitate (see Section
6.5.1). It then is quite difficult to determine the magnitude of the solubility.
Many ‘‘structural’’ proteins, i.e., those that provide mechanical
properties to a system, have a very poor solubility. This is at least partly
due to very large size. The water insoluble glutelins of wheat flour consist of
peptides that are cross-linked by 22 S 22 S 22 bridges into very large molecules
(they are, moreover, rather hydrophobic). Most structural proteins are
fibrous. Collagen, the main component of tendon and also abundant in skin,
cartilage, and bone, largely consists of triple helices of long peptides. The
helices are closely packed to form fibrils, in which they are covalently
bonded to each other. Such a material is completely insoluble. When
collagen is boiled in water, many of the covalent bonds are broken
(including some peptide bonds) and the helices unfold. In this way gelatin is
obtained, and gelatin is well soluble (at least at temperatures above 30 8 C),
because it has very few hydrophobic amino acid residues. (See Section 17.2.2
for more about gelatin as a gelling agent.)