Hair Damage 382 added or higher temperatures reached. Nevertheless, even though the experimental data are satisfactorily described by this one-step model, the real mechanism of denaturation can be more complex. Transformation of a protein between various conformational states might be brought about by changes in temperature, pressure, pH, ligand concentration, chemical denaturants or other solvent changes. A transformation may only come about if the folded and unfolded states have different affinities for these parameters. Temperature-induced protein unfolding (at equilibrium) arises from differences in enthalpy (ΔH) between folded and unfolded states pressure denaturation can only occur if the folded and unfolded states have different partial molar volumes (the unfolded state is normally of lower volume) unfolding at high or low pH implies differences in pK A of protein acidic or basic groups ligand-induced unfolding or stabilization of the native fold results from differences in binding affinity of the ligand regarding folded or unfolded states chemical denaturants may act as ligands, binding differently to folded or unfolded states, or may act indirectly via changes in overall solvent properties. In addition, there are modifiers (sensitizers and protectants) for denaturation mechanisms. In the case of heat denaturation, pH is known to accentuate heat denaturation in individual proteins. Other hyperthermic sensitizers in cells include methanol, ethanol, propanol, and butanol. Other agents (thiol- specific oxidative agents) can also sensitize protein to denaturation. There are also agents such as glycerol, and D 2 O, as well as other proteins (called Heat Shock Proteins [HSPs]) that can retard or delay protein denaturation in cells. If a particular ligand binds strongly to the native protein but less well to the unfolded chain, it results in a shift of the unfolding transition temperature (T m ) upwards with increasing ligand concentration [L] until the concentration is such that both N and U are fully liganded. The effect of varying pH on the stability of protein folding is just a special case of the ligand binding consequences described above. In this case the ligands are aqueous hydrogen ions (H+) that bind to specific protein sites (acidic or basic groups) in