title: Selective partitioning of cholesterol and a model drug into liposomes of varying size.
abstract: The resistance of a lipid bilayer with respect to a bending deformation generally depends on the presence of membrane additives such as sterols, cosurfactants, peptides, and drugs. As a consequence, the partitioning of membrane additives into liposomes becomes selective with respect to liposome size; i.e., membrane rigidification depletes the membrane additives in the smaller (more strongly curved) liposomes. We have measured this liposome size-selective partitioning for two membrane additives - cholesterol and the porphyrin-based photosensitizer temoporfin - using asymmetrical flow field-flow fractionation (AF4) of liposomes and radioactive labeling of the membrane additive and lipid. The method yields either the molar cholesterol-to-lipid or the temoporfin-to-lipid ratio as a function of liposome size, from which we calculate the corresponding change of the membrane bending stiffness. For small unilamellar fluid-phase liposomes composed of palmitoyloleoylphosphatidylcholine (POPC) and palmitoyloleoylphosphatidylglycerol (POPG), we find that cholesterol rigidifies the host membrane in a manner consistent with previously reported measurements. In contrast, temoporfin softens this membrane. Partitioning results for gel-phase liposomes composed of dipalmitoylphosphatidylcholine (DPPC) and dipalmitoylphosphatidylglycerol (DPPG) are also curvature-sensitive but cannot be interpreted on the basis of the bending stiffness alone.
authors.affiliation: Friedrich Schiller University Jena, Department of Pharmaceutical Technology, Lessingstrasse 8, D-07743 Jena, Germany. christiane.decker@uni-jena.de
authors.forename: Christiane
authors.initials: C
authors.lastname: Decker
authors.forename: Alfred
authors.initials: A
authors.lastname: Fahr
authors.forename: Judith
authors.initials: J
authors.lastname: Kuntsche
authors.forename: Sylvio
authors.initials: S
authors.lastname: May
mesh_terms: D002784:Cholesterol / Q000737:chemistry*; D031521:Fractionation, Field Flow; D008081:Liposomes / Q000737:chemistry*; D055595:Mechanical Phenomena; D008652:Mesoporphyrins / Q000737:chemistry*; D008962:Models, Theoretical; D009995:Osmosis; D017319:Photosensitizing Agents / Q000737:chemistry*
chemical_list: D008081:Liposomes; D008652:Mesoporphyrins; D017319:Photosensitizing Agents; D002784:Cholesterol; C072269:temoporfin