A Membrane Biophysics Perspective on the Mechanism of Alcohol Toxicity.

Motivations for understanding the underlying mechanisms of alcohol toxicity range from economical to toxicological and clinical. On the one hand, acute alcohol toxicity limits biofuel yields, and on the other hand, acute alcohol toxicity provides a vital defense mechanism to prevent the spread of disease. Herein the role that stored curvature elastic energy (SCE) in biological membranes might play in alcohol toxicity is discussed, for both short and long-chain alcohols. Structure-toxicity relationships for alcohols ranging from methanol to hexadecanol are collated, and estimates of alcohol toxicity per alcohol molecule in the cell membrane are made. The latter reveal a minimum toxicity value per molecule around butanol before alcohol toxicity per molecule increases to a maximum around decanol and subsequently decreases again. The impact of alcohol molecules on the lamellar to inverse hexagonal phase transition temperature (TH) is then presented and used as a metric to assess the impact of alcohol molecules on SCE. This approach suggests the nonmonotonic relationship between alcohol toxicity and chain length is consistent with SCE being a target of alcohol toxicity. Finally, in vivo evidence for SCE-driven adaptations to alcohol toxicity in the literature are discussed.