SIMULATION OF WATER TRANSPORT THROUGH A LIPID-MEMBRANE

To obtain insight in the process of water permeation through a lipid m embrane, we performed molecular dynamics simulations on a phospholipid (DPPC)/water system with atomic detail. Since the actual process of p ermeation is too slow to be studied directly, we deduced the permeatio n rate indirectly via computation of the free energy and diffusion rat e profiles of a water molecule across the bilayer. We conclude that th e permeation of water through a lipid membrane cannot be described ade quately by a simple homogeneous solubility-diffusion model. Both the e xcess free energy and the diffusion rate strongly depend on the positi on in the membrane, as a result from the inhomogeneous nature of the m embrane. The calculated excess free energy profile has a shallow slope and a maximum height of 26 kJ/mol. The diffusion rate is highest in t he middle of the membrane where the lipid density is low. In the inter facial region almost all water molecules are bound by the lipid headgr oups, and the diffusion turns out to be 1 order of magnitude smaller. The total transport process is essentially determined by the free ener gy 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) x 10(-2) cm/s at 350 K, comparable to exper imental 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 realist ic than the ''two-phase'' solubility-diffusion model.