SOLUTE DIFFUSION IN LIPID BILAYER-MEMBRANES - AN ATOMIC-LEVEL STUDY BY MOLECULAR-DYNAMICS SIMULATION

To elucidate the mechanism of solute diffusion through lipid bilayer m embranes, nearly 4 ns of molecular dynamics simulations of solutes in phospholipid bilayers was conducted. The study, the first atomic level study of solute diffusion in a lipid bilayer, involved four simulatio ns of an all-atom representation of a fully solvated dimyristoylphosph atidylcholine (DMPC) bilayer in the Lalpha phase with benzene molecule s as solutes, totaling over 7100 atoms. These simulations agree with e xperimental evidence that the presence of small solutes does not affec t bilayer thickness but does result in slight perturbations in the ord ering of the hydrocarbon chains. At room temperature, the benzene mole cules have essentially isotropic motion and rotate freely. The rate of translational diffusion varies with position within the bilayer and i s faster in the center than near the zwitterionic headgroups and is in excellent agreement with experimental values for the diffusion of sma ll solutes in a bilayer. These simulations have elucidated the mechani sm of diffusion in a bilayer to be similar to the ''hopping'' mechanis m found for the diffusion of gases through soft polymers. Jumps of up to 8 angstrom can occur in as little as 5 ps whereas average motions f or that time period are only approximately 1.5 angstrom. In many cases , the jumps are moderated by torsional changes in the hydrocarbon chai ns which serve as ''gates'' between voids through which the benzene mo lecules move. Comparison of these simulations with another 1000-ps sim ulation of benzene in a pure alkane provides evidence that lipid bilay ers should not be treated as a homogeneous bulk hydrocarbon phase.