title: Influence of chain ordering on the selectivity of dipalmitoylphosphatidylcholine bilayer membranes for permeant size and shape.
abstract: The effects of lipid chain packing and permeant size and shape on permeability across lipid bilayers have been investigated in gel and liquid crystalline dipalmitoylphosphatidylcholine (DPPC) bilayers by a combined NMR line-broadening/dynamic light scattering method using seven short-chain monocarboxylic acids (formic acid, acetic acid, propionic acid, butyric acid, valeric acid, isovaleric acid, and trimethylacetic acid) as permeants. The experimental permeability coefficients are compared with the predictions of a bulk solubility diffusion model in which the bilayer membrane is represented as a slab of bulk hexadecane. Deviations of the observed permeability coefficients (Pm) from the values predicted from solubility diffusion theory (Po) lead to the determination of a correction factor, the permeability decrement f (= Pm/Po), to account for the effects of chain ordering. The natural logarithm of f has been found to correlate linearly with the inverse of the bilayer free surface area with slopes of 25 +/- 2, 36 +/- 3, 45 +/- 8, 32 +/- 12, 33 +/- 4, 49 +/- 12, and 75 +/- 6 A2 for formic acid, acetic acid, propionic acid, butyric acid, valeric acid, isovaleric acid, and trimethylacetic acid, respectively. The slope, which measures the sensitivity of the permeability coefficient of a given permeant to bilayer chain packing, exhibits an excellent linear correlation (r = 0.94) with the minimum cross-sectional area of the permeant and a poor correlation (r = 0.59) with molecular volume, suggesting that in the bilayer interior the permeants prefer to move with their long principal axis along the bilayer normal. Based on these studies, a permeability model combining the effects of bilayer chain packing and permeant size and shape on permeability across lipid membranes is developed.
authors.affiliation: Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, Utah 84112 USA.
authors.forename: T X
authors.initials: TX
authors.lastname: Xiang
authors.forename: B D
authors.initials: BD
authors.lastname: Anderson
mesh_terms: D015060:1,2-Dipalmitoylphosphatidylcholine / Q000737:chemistry*; D055592:Biophysical Phenomena; D001703:Biophysics; D002264:Carboxylic Acids / Q000737:chemistry; D004058:Diffusion; D066298:In Vitro Techniques; D008027:Light; D008051:Lipid Bilayers / Q000737:chemistry*; D008081:Liposomes / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008956:Models, Chemical; D008958:Models, Molecular; D008968:Molecular Conformation; D010539:Permeability; D012542:Scattering, Radiation; D012995:Solubility; D013499:Surface Properties; D013816:Thermodynamics
chemical_list: D002264:Carboxylic Acids; D008051:Lipid Bilayers; D008081:Liposomes; D015060:1,2-Dipalmitoylphosphatidylcholine