Molecular mechanism of flip-flop in triple-layer oleic-acid membrane: Correlation between oleic acid and water

We perform all-atom molecular dynamics simulations to study a pure oleic acid (OA) membrane in water that results in a triple-layer structure. We compute the pressure profiles to examine the hydrophobic and hydrophilic regions, and to estimate the surface tension (≈34.5 mN/m), which is similar to those of lipid membranes. We observe that the membrane of OAs having a large diffusion coefficient (0.4 × 10^-7 cm²/s) along the normal to the membrane is an ideal model to study oleic acid flip-flop. In the model, the membrane contains a middle layer serving as an intermediate for water and OAs to easily migrate (flip-flop) from one to other leaflets. Water molecules surrounding OA head-groups help to reduce the barriers at the hydrophobic interface to trigger flip-flop events. Within 500 ns, we observe 175 flip-flop events of OAs and 305 events of water traversing the membrane. The ratio of water passing rate (k_H2O = 0.673 ns^-1) to OA flip-flop rate (k_OA = 0.446 ns^-1) is 3/2. The ratio of the totally correlated water-OA events to the totally uncorrelated water-OA events, n _cor/nuncor, is also 3/2. The probability of the totally and partially correlated events is 69%. The results indicate that the trans-membrane movement of water and OAs is cooperative and correlated, and agrees with experimentally measured absorption rates. They support the idea that OA flip-flop is more favorable than transport by means of functional proteins. This study might provide further insight into how primitive cell membranes work, and how the interplay and correlation between water and fatty acids may occur.