Thermodynamics of flip-flop and desorption for a systematic series of phosphatidylcholine lipids

We have investigated the thermodynamics of phospholipid flip-flop and desorption. Using a series of PC (phosphatidylcholine) lipids with different lengths of acyl tails, and number of unsaturated tails, we calculated potentials of mean force (PMFs) in atomistic molecular dynamics simulations. The PMFs describe the free energy for moving a single lipid molecule from water to the center of the respective lipid bilayer. The free energy to move the lipid from equilibrium to the bilayer center is assumed to be the free energy barrier for lipid flip-flop. We find that the free energy barrier for flip-flop is strongly dependent on the structure of the bilayer; ranging from 16 kJ mol(-1) in the thin DLPC bilayer, to 90 kJ mol(-1) in the DOPC bilayer. There are large deformations in the bilayers' structure, to accommodate the charged PC head group in the bilayer interior. We observe pore formation in all the bilayers, except for POPC and DOPC. The free energy for desorption is equal to the excess chemical potential of the lipid in the bilayer compared to bulk water. The increased chemical potential for PC lipids with longer acyl tails is in qualitative agreement with the critical micelle concentrations. We also determined PMFs for transferring water into the center of the series of lipid bilayers. Water has the same free energy of transfer to the center of all the bilayers, indicating the lipid PMFs differ due to bilayer deformations. Lipid bilayers are soft and deformable, allowing large structural changes, which are dependent on the composition of the bilayer. Our results show that similar PC lipids with only slightly different acyl tails, can have dramatically different thermodynamic behavior.