Characterization of lipid membrane dynamics by simulation .3. Probing Molecular transport across the phospholipid bilayer

Purpose, The goal of this study is to elucidate the role of the motions of the hydrocarbon chains of a phospholipid bilayer in penetrant diffusion. Penetrant size, as well as its position in the hydrocarbon core of the lipid bilayer, has also been explored regarding impact on the diffusion rate in a phospholipid bilayer. Method. Molecular dynamics, MD, simulations were carried out on a model dimyristoyl phosphatidylcholine (DMPC) membrane bilayer with and without methanol and propanol as penetrants. The MD trajectories were analyzed in terms of estimating time and space properties. Results. These simulations show that torsion angle kink shifts in the hydrocarbon chains of phospholipids are natural occurrences in a bilayer assembly. The diffusion coefficients of methanol and propanol in a DMPC lipid bilayer, as calculated from the MD simulations, agree with experimental measurements. Both methanol and propanol show different diffusion rates in different regions of the hydrocarbon chain matrix of the lipid bilayer. Solute size has more impact on diffusion rate in the bilayer regions with high torsion angle order parameters, as compared to the regions with low torsion angle order parameters. Conclusions. The simulated transport behavior suggests that a kink shift diffusion mechanism is more likely to occur in regions with high torsion angle order parameters, and a free volume transport mechanism is more likely operative in the region with low torsion angle order parameters, mainly the center core of the bilayer. A three zone diffusion model is proposed for transport of a penetrant across a bilayer.