The cut-off effect of n-alcohols in lipid rafts: A lipid-dependent phenomenon

n-Aliphatic alcohols act as anesthetics only up to a certain chain length, beyond which its biological activity disappears. This is known as the ‘cut-off’ phenomenon. Although the most accepted explanation is based on action sites in membrane proteins, it is not well understood why alcohols alter their functions. The structural dependence of these protein receptors to lipid domains known as ‘lipid rafts’, suggests a new approach to tackle the puzzling phenomenon. In this work, by performing molecular dynamic simulations (MDS) to explore the lipid role, we provide relevant molecular details about the membrane-alcohol interaction at the cut-off point regime. Since the high variability of the cut-off points found on protein receptors in neurons may be a consequence of differences in the lipid composition surrounding such proteins, our results could have a clear-cut importance. [Display omitted] •Molecular dynamic simulations (MDS) explore the lipid role in the cut-off phenomenon.•The alcohol effect on lipid membranes is highly sensitive to the lipid backbone and the carbon chain length.•The cut-off phenomenon of n-alcohols could be related to the anaesthesia mechanism.