The Enthalpy of Acyl Chain Packing and the Apparent Water-Accessible Apolar Surface Area of Phospholipids

AbstractThe energetics of phospholipid aggregation depend on the apparent water-accessible apolar surface area (ASAap), ordering effects of the chains, and headgroup interactions. We quantify the enthalpy and entropy of these interactions separately. For that purpose, the thermodynamics of micelle formation of lysophosphatidylcholines (LPCs, chains C10, C12, C14, and C16) and diacylphosphatidylcholines (DAPCs, chains C5, C6, and C7) are studied using isothermal titration calorimetry. The critical micelle concentration (CMC) values are 90, 15, and 1.9mM (C5–C7-DAPC) and 6.8, 0.71, 0.045, and 0.005mM (LPCs). The group contributions per methylene of ΔΔG0=−3.1 kJ/mol and ΔΔCP=−57 J/(mol · K) for LPCs agree with literature data on hydrocarbons and amphiphiles. An apparent deviation of DAPCs (−2.5 kJ/mol, 45 J/(mol · K)) is due to an intramolecular interaction between the two chains, burying 20% of the surface. The chain/chain interaction enthalpies in a micelle core are by ∼−2 kJ/(mol) per methylene group more favorable than in bulk hydrocarbons. We conclude that the impact of the chain conformation and packing on the interaction enthalpy is very pronounced. It serves to explain a variety of effects reported on membrane binding. Interactions within the water-accessible region show considerable ΔH, but almost no ΔG0. The heat capacity changes suggest about three methylene groups (ASAap ≈ 100Å2) per LPC remain exposed to water in a micelle (DAPC: 2 CH2/70Å2)