Molecular Dynamics simulation of Immobilized Artifical Membranes

A 250 ps molecular dynamics (MD) simulation of an immobilized artificial membrane (IAM) surface was performed and compared to previous MD simulations of fluid membranes. Experimentally, IAM surfaces are prepared by immobilizing monolayers of membrane lipids and, consequently, IAM surfaces are distinct from the surfaces found in fluid membranes. The computer-generated IAM surface used for the simulation contained 36 phosphatidylcholine (PC) molecules and 2487 water molecules. In addition, seven straight chain alkanes were intercalated between the 36 PC molecules to simulate the experimental end capping performed during the synthesis of IAMs. The interfacial distributions of glycerol phosphocholine atoms were compared for both immobilized and fluid membranes. MD simulations indicate that the distribution of glycerol phosphocholine atoms is virtually identical in both fluid and immobilized membranes. This indicates that the polar interfacial region of the IAM surface is very similar to the polar interfacial region of fluid membranes. Water molecules are strongly polarized at the IAM interfacial region. Water polarization decays experimentally from the first hydration layer to bulk water with a decay length of 13 Å. Water did not penetrate into the hydrophobic alkyl chains of the IAM interphase during the 250 ps simulation. Water diffusion near the glycerolphosphocholine head groups, calculated from the 250 ps simulation, is twice as fast in the plane of the membrane as compared to the direction that is normal to the membrane. The internal phosphate diffusion constant calculated from a 250 ps trajectory was 1.7 ns^-1 which is similar to the value of 1 ns^-1 experimentally determined by NMR. Order parameters calculated from the trajectory demonstrated that hydrocarbon chains are more ordered in IAMs compared to fluid membranes. Collectively, these results suggest that the polar interfacial region of the IAM surface mimics well the polar interfacial region of fluid membranes, but the hydrocarbon part of the IAM surface has unique physicochemical properties compared to fluid membranes. The similarities between the physicochemical properties of IAMs and fluid membranes at the membrane interface explain, in part, why IAMs can be used to measure membrane partition coefficients for drugs and solutes.