Enhanced Hydrophobicity of Fluorinated Lipid Bilayer: A Molecular Dynamics Study

Hiroaki Saito, Wataru Shinoda, and Masuhiro Mikami

J. Phys. Chem. B 112, 11305-11309 (2008).

A molecular dynamics simulation of a partially fluorinated phospholipid bilayer has been carried out to understand the effect of fluorination of the hydrophobic chains on the structure and water permeability across the membrane. The fluorocarbon chains typically have the all-trans conformation, showing highly ordered structure in the membrane core compared with ordinary hydrocarbon chains. The free energy profiles of water across the bilayers are successfully estimated by a revised cavity insertion Widom method. The fluorinated bilayer shows higher free energy barrier than the ordinary non-fluorinated lipid bilayer by about 1.2 kcal/mol, suggesting a significantly lower water permeability of the fluorinated bilayer membrane. The cavity distribution analysis elucidates the reduced free volume in the fluorinated membrane due to the neatly packed chains, which should account for the higher free energy barrier.