Simulation of water transport through a lipid membrane

Abstract

To obtain insight in the process of water permeation through a lipid membrane, we performed molecular dynamics simulations on a phospholipid (DPPC)/water system with atomic detail. Since the actual process of permeation is too slow to be studied directly, we deduced the permeation rate indirectly via computation of the free energy and diffusion rate profiles of a water molecule across the bilayer. We conclude that the permeation of water through a lipid membrane cannot be described adequately by a simple homogeneous solubility-diffusion model. Both the excess free energy and the diffusion rate strongly depend on the position in the membrane, as a result from the inhomogeneous nature of the membrane. The calculated excess free energy profile has a shallow slope and a maximum height of 26 kJ/mol. The diffusion rate is highest in the middle of the membrane where the lipid density is low. In the interfacial region almost all water molecules are bound by the lipid headgroups, and the diffusion turns out to be 1 order of magnitude smaller. The total transport process is essentially determined by the free energy barrier. The rate-limiting step is the permeation through the dense part of the lipid tails, where the resistance is highest. We found a permeation rate of 7(±3) × 10-2 cm/s at 350 K, comparable to experimental values for DPPC membranes, if corrected for the temperature of the simulation. Taking the inhomogeneity of the membrane into account, we define a new “four-region” model which seems to be more realistic than the “two-phase” solubility-diffusion model.