8.6. Self-assembly in cells[[Student version, January 17, 2003]] 289
also noted that proteins can be denatured by transfering them to nonpolar solvents, in which the
hydrophobic interaction is absent. Finally, adding even extremely small concentrations of surfac-
tants (for example, 1% SDS) can also unfold proteins. We can interpret this fact by analogy with
the solubilization of membranes (Figure 8.8 on page 285): The surfactants can shield hydrophobic
regions of the polypeptide chain, reducing their tendency to asociate with each other. For these
and other reasons,hydrophobic interactions are believed to give the dominant force driving protein
folding.
Other interactions can also help determine a protein’s structure. A charged residue, like the
ones studied in Section 8.3.3 on page 273, will have a Born self-energy. Such residues will prefer to
sit at the surface of the folded protein, facing the highly polarizable exterior water (see Section 7.5.2
on page 243), rather than being buried in the interior. Positive residues will also seek the com-
pany of negatively charged ones, and avoid other positive charges. While significant, these specific
interactions are probably not as important as the hydrophobic effect. For example, if we titrate a
protein to zero net charge then its stability is found not to depend very much on the surrounding
salt concentration, even though salt weakens electrostatic effects (see Idea 7.28).
Aggregation Besides supplyingintramolecular forces driving folding, hydrophobic interactions
also giveintermolecular forces, which can stick neighboring macromolecules together. Chapter 7
mentioned the example of microtubules, whose tubulin monomers are held together in this way.
Section 8.3.4 on page 275 gave another example: Sickle-cell anemia’s debilitating effects stem from
the unwanted hydrophobic aggregation of defective hemoglobin molecules. Cells can even turn their
macromolecules aggregating tendencies on and off to suit their needs. For example, your blood
contains a structural protein called fibrinogen, which normally floats in solution. When a blood
vessel gets injured, however, the injury triggers an enzyme that clips off a part of the fibrinogen
molecule, exposing a hydrophobic patch. The truncated protein, called fibrin, then polymerizes to
form the scaffold on which a blood clot can form.
Hydrophobic aggregation is not limited to the protein–protein case. Chapter 9 will also identify
hydrophobic interactions as key to stabilizing the double-helical structure of DNA. Each basepair
is shaped like a flat plate; both of its surfaces are nonpolar, and so it is driven to stick onto the
adjoining basepairs in the DNA chain, forming a twisted stack. Hydrophobic interactions also
contribute to the adhesion of antibodies to their corresponding antigens.
8.6.3 Another trip to the kitchen
This has been a long, detailed chapter. Let’s take another trip to the kitchen.
Besides being a multibillion dollar industry, food science nicely illustrates some of the points
made in this chapter. For example, Your Turn 5a on page 142 caricatured milk as a suspension of
fat droplets in water. Actually, milk is far more sophisticated than this. In addition to the fat and
water, milk contains two classes of proteins, Miss Muffet’s curds (the casein complex) and whey
(mainlyα-lactalbumin andβ-lactoglobulinlactoglobulins). In fresh milk the casein complexes self-
assemble into micelles of radius around 50nm.The micelles are kept apart in part by electrostatic
repulsion (see Section 7.4.4 on page 237), and so the milk is fluid. However, minor environmental
changes can induce curdling, a coagulation (clumping) of the micelles into a gel (Figure 8.10).
In the case of yogurt, the growth of bacteria such asLactobacillus bulgaricusandStreptococcus
thermophiluscreates lactic acid as a waste product (alternatively you can add acid by hand, for