MODULATION OF LIPID PHASE-BEHAVIOR BY KOSMOTROPIC AND CHAOTROPIC SOLUTES - EXPERIMENT AND THERMODYNAMIC THEORY

By means of differential scanning calorimetry and from a review of pub lished data we demonstrate in this work that low-molecular weight kosm otropic substances (water-structure makers) of different chemical stru cture such as disaccharides, proline, and glycerol have identical effe cts on the phase behavior of several kinds of phospholipids and glycol ipids. These substances favor formation of the high-temperature invert ed hexagonal phase (HII) and the low-temperature lamellar crystalline (L(c)) and gel (L(beta)) phases at the expense of the intermediate lam ellar liquid-crystalline phase (L(alpha)). The latter phase may comple tely disappear from the phase diagram at high enough solute concentrat ion. By contrast, chaotropic substances (water-structure breakers) suc h as sodium thiocyanate and guanidine hydrochloride expand the existen ce range of L(alpha) at the expense of the adjacent L(beta) and H-II p hases. Moreover, chaotropes are able to induce the appearance of missi ng intermediate liquid-crystalline phases in lipids displaying direct L(beta) --> H-II transitions in pure water. In previous publications w e have considered the influence of chaotropic and kosmotropic substanc es on the lipid phase behavior as a manifestation of their indirect (H ofmeister) interactions with the lipid aggregates. For a quantitative characterization of this effect, here we derive a general thermodynami c equation between lipid phase transition temperature and solute conce ntration, analogous to the Clapeyron-Clausius equation between transit ion temperature and pressure. It provides a clear description in physi cal quantities of the disparate effects of kosmotropic and chaotropic substances on the relative stability of the lipid-water phases. Accord ing to this equation, the magnitude of the solute effect is proportion al to the hydration difference of the adjacent lipid phases and invers ely proportional to the transition latent heat. The sign and magnitude of the transition shifts depend also on the degree of solute depletio n (for kosmotropes) or enrichment (for chaotropes) at the interfaces, in comparison to the solute concentration in bulk water.