Both the permeability coefficients (Pd‘s) through lipid bilayer membranes of varying composition (lecithin [L], lecithinxholesterol [LC], and sphingomyelin :cholesterol [SC]) and the n-hexadecane:water partition coefficients (Khc’s) of H20 and seven nonelectrolytes (1,6 hexanediol, 1,4 butanediol, n-butyramide, isobutyramide, acetamide, formamide, and urea) were measured. For a given membrane composition, Pd/DKhc (where D is the diffusion constant in water) is the same for most of the molecules tested. There is no extraordinary dependence of Pd on molecular weight; thus, given (acetamide), Pd(1,6 hexanediol) is correctly predicted from the Khc and D values for the two molecules. The major exceptions are H20, whose value of PdIDKhc is about 10-fold larger, and urea, whose value is about 5-fold smaller than the general average. In a "tight" membrane such as SC, pd(n-butyramide/Pdisobutyramide) = 2.5; thus this bilayer manifests the same sort of discrimination between branched and straight chain molecules as occurs in many plasma membranes. Although the absolute values of the Pds change by more o than a factor of 100 in going from the tightest membrane (SC) to the loosest (L), the relative values remain approximately constant. The general conclusion of this study is that H20 and nonelectrolytes cross lipid bilayer membranes by a solubility-diffusion mechanism, and that the bilayer interior is much more like an oil (a la Overton) than a rubber-like polymer (á la Lieb and Stein).
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