Thermodynamics of phospholipid self-assembly.

Negatively charged phospholipids are an important component of biological membranes. The thermodynamic parameters governing self-assembly of anionic phospholipids are deduced here from isothermal titration calorimetry. Heats of demicellization were determined for dioctanoyl phosphatidylglycerol (PG) and phosphatidylserine (PS) at different ionic strengths, and for dioctanoyl phosphatidic acid at different pH values. The large heat capacity (ΔC°(P) ∼ -400 J.mol(-1) K(-1) for PG and PS), and zero enthalpy at a characteristic temperature near the physiological range (T(∗) ~ 300 K for PG and PS), demonstrate that the driving force for self-assembly is the hydrophobic effect. The pH and ionic-strength dependences indicate that the principal electrostatic contribution to self-assembly comes from the entropy associated with the electrostatic double layer, in agreement with theoretical predictions. These measurements help define the thermodynamic effects of anionic lipids on biomembrane stability.