Interlamellar forces and the thermodynamic characterization of lamellar phospholipid systems

In this review, we summarize a series of experimental studies of the swelling of zwitterionic lamellar phospholipid and phospholipid-cholesterol systems using a novel double twin calorimeter. With this method, one can obtain simultaneous measures of the partial molar free energy and the partial molar enthalpy, and the experimental studies thus provide a complete thermodynamic characterization of the isothermal swelling process. A major finding is that the swelling of lamellar zwitterionic phospholipid systems at higher water contents (> 4 water molecules per lipid) is endothermic. The enthalpy has the opposite sign relative to the free energy, thus demonstrating that the swelling process is entropy driven. The water uptake also triggers a transition from a gel to a liquid crystalline state showing that, at given water content, the swelling pressure is much higher in the liquid crystal than in the gel. When cholesterol is added to the system the liquid ordered phase is formed at all available water contents. In this phase the swelling pressure varies smoothly and takes relatively low values at water contents below two per phospholipid, while it is substantially higher than in the gel phase at higher water contents. Together, these data demonstrate that the swelling pressure is sensitive to the phase state of the lipids. We also describe a series of studies that demonstrate that the addition of a second polar solute to the phospholipid–water system has a remarkably small effect on the swelling behavior when analyzed with respect to solvent volume. The reviewed experimental studies provide a thermodynamic characterization of the swelling of lamellar zwitterionic phospholipid systems that should be encompassed in the mechanistic molecular interpretation of the “hydration force.”

Graphical abstractSimultaneously measured partial molar enthalpy of water, Δhw, and chemical potential of water, Δμw in the region of swelling of the dipalmitoyl phosphatidyl choline gel phase (left), dilauroyl phosphatidyl choline liquid crystalline phase (right), demonstrating that swelling in these systems is entropy driven.Figure optionsDownload full-size imageDownload high-quality image (135 K)Download as PowerPoint slideHighlights► The swelling of lamellar systems has been studied using a double twin calorimeter that provides simultaneous measures of free energy and enthalpy. ► The swelling process is entropy driven at higher water contents. This is consistent with the general conjecture by Israelachvili and Wennertröm. ► There is a systematic interrelation between the quantitative characteristics of the interbilayer interaction and the state of the lipid chains. ► Based on the swelling in mixed polar solvents, one can rule out specific water structure effects as a generic cause of the interlamellar repulsion.