MECHANISM OF SOLUTE DIFFUSION THROUGH LIPID BILAYER-MEMBRANES BY MOLECULAR-DYNAMICS SIMULATION

This study extends previous studies of the mechanism of small molecule diffusion through lipid membranes. Atomic level molecular dynamics si mulations of over 4 ns of benzene in fully hydrated dimyristoylphospha tidylcholine (DMPC) bilayers were performed at four different temperat ures above the gel-to-la phase transition temperature. These studies c onfirm previous observations that small solutes diffuse at different r ates in different locations in the bilayer. This difference in diffusi on is likely to be due to ''jumps'' (single, large movements) between voids which are most common in the center of the bilayer. The benzene molecules appear to favor different regions of the bilayer at differen t temperatures. Although at 320 K the solutes show no regional prefere nce, at 310 K they migrate to the center of the bilayer, while at 340 K they reside mostly near the head group region. This correlates with the distribution of free volume which concentrates at the bilayer cent er at low temperature but becomes more diffuse at higher temperatures. The mechanism of the diffusional process was found to be complex. Not only does the rate of diffusion depend on location within the bilayer , but the characteristics of this process appear to respond to tempera ture changes differently in the different regions of the bilayer. Only short time motions are dependent directly on the temperature. Longer time motions depend additionally on the size and availability of voids and the rate of torsional isomerization of the lipid molecules. It wa s found that an increase in kinetic energy was not always coincident w ith a jump; some jumps may be passive processes. This study provides f urther evidence that the interior of lipid bilayer membranes is not a homogeneous system analogous to pure alkane. Rather it is a structured system with different properties depending on the distance from the l ipid/water interface.