Establishment of the Meyer-Overton correlation in an artificial membrane without protein

The potency of anesthetics with various structures increases exponentially with lipophilicity, which is the Meyer-Overton (MO) correlation discovered over 120 years ago. The MO correlation was also observed with various biological effects and chemicals, including alcohols; thus, the correlation represents a fundamental relationship between chemicals and organisms. The MO correlation was explained by the lipid and protein theories, although the principle remains unknown because these are still debating.

The gentle hydration method was used to form giant unilamellar vesicles (GUVs) consisting of high- and low-melting phospholipids and cholesterol in the presence of n-alcohols (C₂-C₁₂). Confocal fluorescence microscopy was used to determine the percentage of GUVs with domains in relation to the n-alcohol concentrations.

n-Alcohols inhibited the domain formation of GUVs, and the half inhibitory concentration (IC₅₀) in the aqueous phase (C_w) decreased exponentially with increasing chain length (lipophilicity). In contrast, the membrane concentrations (C_m) of alcohols for the inhibition, which is a product of the membrane-water partition coefficient and the IC₅₀ values, remained constant irrespective of the chain length.

The MO correlation is established in GUVs, which supports the lipid theory. When alcohols reach the same critical concentration in the membrane, similar biological effects appear irrespective of the chain length, which is the principle underlying the MO correlation.

The protein theory states that a highly lipophilic compound targets minor membrane proteins due to the low C_w. However, our lipid theory states that the compound targets various membrane proteins due to the high C_m.