Role of chain length in the penetration and clustering dynamics of 1-alkanols in lipid bilayer membranes.

Abstract

1-alkanols are well known to have anesthetic and penetration properties, though the mode of operation remains enigmatic. We perform extensive atomistic molecular dynamics simulation to study the penetration of 1-alkanols of different chain lengths in the dioleoyl-phosphatidylcholine (DOPC) bilayer model membrane. Our simulations show that the depth of penetration of 1-alkanol increases with chain length, n, and the deuterium order of the DOPC tail decreases with the chain length of the acyl-chain of the 1-alkanol. We find a cutoff value for the length of the acyl-chain of 1-alkanol, n=12, where 1-alkanol with a chain length greater than the cutoff value takes longer to penetrate the membrane. Our simulation study also demonstrates that the membrane exhibits clusters of 1-alkanols with acyl chains longer than the cutoff value, whereas 1-alkanols with acyl-chain shorter than the cutoff value are distributed homogeneously in the membrane and penetrate the membrane in a shorter time than longer-acyl-chain 1-alkanols. These findings add to our understanding of the anomalies in anesthetic molecule partitioning in the cell membrane and may have implications for general anesthesia.