It is worth mentioning that, besides the beta-sheet structure leading a chain-
folding of protein molecules, certain regular polypeptide sequences are viable to
form an alfa-helix structure, i.e. the oxygen atom on the carbonyl group of each
amino-acid residue forming a hydrogen bonding with the hydrogen atom on the
amino group of the fourth amino-acid residue along the chain. The coil-helix
transition, in principle, corresponds to one-dimensional Ising lattice model, imply-
ing no behavior of phase transitions. Higher temperatures favor the formation of the
alfa-helix, thus helix formation makes a positive contribution to the enthalpy
change, unfavorable to the decrease of total free energy. Even with a significant
conformational entropy loss, the driving force for helix formation may come from a
synergetic result of entropy gain by releasing the adsorbed water molecules,
corresponding to the LCST type of phase separations. The hydrophobic interactions
coming from the similar synergetic source also make unfolding of the native-state
proteins under lower temperatures, and thus losing their living activities. At further
higher temperatures, the helix structures make spontaneous unwinding, like the
denaturing of native-state proteins at high temperatures (Nelson 2004 ),
corresponding to the UCST type of phase separation.
In the living cells, the folding process of nascent polypeptides sometimes needs
the cooperative work of molecular chaperones to improve the local microscopic
environment. For instance, chaperones can temporarily screen off the exposure of
hydrophobic residues in the intermediate states of folding, to avoid the aggregation
of protein molecules under the environment of macromolecular crowding in the
cells (Ellis 1997 ). A misfolding of protein molecules may lead to their aggregation
to form an amyloid-fiber structure rich with beta-foldings and thus losing their
living activities. Many senile degenerative diseases of nervous systems are related
to the misfolding of protein molecules, such as Alzheimer’s disease, Parkinson’s
disease, Huntington’s disease, prion disease (including the famous mad-cow dis-
ease), and type II diabetes mellitus. Sicklemia is also caused by the hydrophobic
aggregation of misfolding hemoglobin molecules. Learning and controlling the
molecular mechanisms of these diseases are of essential importance for us to find
the effective curing methods. Protein aggregation also has its own positive side.
When the blood vessel is broken, the fibrinogen in the blood will be cut by a certain
enzyme to exposure its hydrophobic segments, and the segments can glue together
to form up a network structure, favoring the blood clotting at the wound and thus
stopping bleeding (Nelson 2004 ).
Protein unfolding is very sensitive to the pH values, temperatures, salt
concentrations and solvent types. Denaturation of food proteins is a common
phenomenon in our food processing. The casein in the milk performs unfolding
in the yoghurt, leading to the thickening of the yoghurt. The inorganic salts also
make the denaturation of egg proteins, which is the coagulation mechanism of
preserved eggs (also called century eggs). Egg white proteins exchange their
disulfide bonds after denaturation upon heating, and thus crosslink to network a
huge amount of water on the preparation of egg custard. The hydrophobic core of
proteins can also be dismissed at the surface of air bubbles in the water, making the
hydrophobic residues face towards the air, like a surfactant stabilizing the interfaces
11.7 Implication of Interplay in Biological Systems 237