The understanding of the penetration and clusterization of 1-alkanol in bilayer membrane: An open outlook based on atomistic molecular dynamics simulation

TL;DR

This study uses atomistic molecular dynamics simulations to analyze how 1-alkanols of varying chain lengths penetrate and cluster within lipid bilayer membranes, revealing length-dependent behaviors relevant to anesthesia mechanisms.

Contribution

It provides new insights into the penetration depth, clustering, and membrane interaction of 1-alkanols based on chain length, highlighting a critical cutoff point affecting their membrane behavior.

Findings

Longer 1-alkanols penetrate deeper into membranes.

Alkanols with chain length >12 form clusters in membranes.

Shorter alkanols distribute homogeneously and penetrate faster.

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 increases with the chain length of the acyl-chain of the 1-alkanol. We find a cut-off value for the length of the acyl-chain of 1-alkanol, n = 12, where 1-alkanol with a chain length greater than the cut-off 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 cut-off value, whereas 1-alkanols with acyl-chain shorter than the cut-off 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.