title: Alcohol's effects on lipid bilayer properties.
abstract: Alcohols are known modulators of lipid bilayer properties. Their biological effects have long been attributed to their bilayer-modifying effects, but alcohols can also alter protein function through direct protein interactions. This raises the question: Do alcohol's biological actions result predominantly from direct protein-alcohol interactions or from general changes in the membrane properties? The efficacy of alcohols of various chain lengths tends to exhibit a so-called cutoff effect (i.e., increasing potency with increased chain length, which that eventually levels off). The cutoff varies depending on the assay, and numerous mechanisms have been proposed such as: limited size of the alcohol-protein interaction site, limited alcohol solubility, and a chain-length-dependent lipid bilayer-alcohol interaction. To address these issues, we determined the bilayer-modifying potency of 27 aliphatic alcohols using a gramicidin-based fluorescence assay. All of the alcohols tested (with chain lengths of 1-16 carbons) alter the bilayer properties, as sensed by a bilayer-spanning channel. The bilayer-modifying potency of the short-chain alcohols scales linearly with their bilayer partitioning; the potency tapers off at higher chain lengths, and eventually changes sign for the longest-chain alcohols, demonstrating an alcohol cutoff effect in a system that has no alcohol-binding pocket.
authors.affiliation: Department of Physiology and Biophysics, Weill Cornell Medical College, New York, New York, USA. hei2001@med.cornell.edu
authors.forename: Helgi I
authors.initials: HI
authors.lastname: Ingólfsson
authors.forename: Olaf S
authors.initials: OS
authors.lastname: Andersen
mesh_terms: D000438:Alcohols / Q000737:chemistry*; D005453:Fluorescence; D005456:Fluorescent Dyes / Q000737:chemistry; D007700:Kinetics; D008051:Lipid Bilayers / Q000737:chemistry*; D000439:Pentanols / Q000737:chemistry
chemical_list: D000438:Alcohols; D005456:Fluorescent Dyes; D008051:Lipid Bilayers; D000439:Pentanols