Miñones J, Pais S, Miñones J, Conde O, Dynarowicz-Łatka P
University of Santiago de Compostela, Faculty of Pharmacy, Department of Physical Chemistry, Campus Sur, 15706 Santiago de Compostela, Spain.
Biophys Chem. 2009 Mar;140(1-3):69-77. doi: 10.1016/j.bpc.2008.11.011. Epub 2008 Dec 3.
This paper is aimed at investigating sterol/phospholipid interactions in the exact proportion that occurs in fungi/mammalian cells. We have performed a thorough analysis of surface pressure (pi)-area (A) isotherms with the Langmuir monolayer technique, complemented with Brewster angle microscopy (BAM) images. The following mixtures were analysed: cholesterol (Chol)-dipalmitoyl phosphatidylcholine (DPPC), Chol-dioleoyl phosphatidylcholine (DOPC), ergosterol (Erg)-DPPC, and Erg-DOPC. For each system, two different concentrations of the sterols were used, 13 and 30%, corresponding to the range of concentration found in various natural membranes. The obtained results show the existence of attractive interactions between phospholipids and cholesterol. Mixtures with ergosterol behave quite differently, i.e. either the interactions are repulsive (mixtures with DPPC) or the system is ideal (mixtures with DOPC). The obtained results have implications in the polyene antibiotics mode of action, i.e. the polyenes may interact easier with ergosterol, present in fungi cells, as compared to cholesterol--the main sterol of the mammalian cellular membranes.
本文旨在研究真菌/哺乳动物细胞中实际存在的甾醇/磷脂相互作用的精确比例。我们使用朗缪尔单层技术对表面压力(π)-面积(A)等温线进行了全面分析,并辅以布鲁斯特角显微镜(BAM)图像。分析了以下混合物:胆固醇(Chol)-二棕榈酰磷脂酰胆碱(DPPC)、Chol-二油酰磷脂酰胆碱(DOPC)、麦角固醇(Erg)-DPPC和Erg-DOPC。对于每个体系,使用了两种不同浓度的甾醇,分别为13%和30%,这与各种天然膜中发现的浓度范围相对应。所得结果表明磷脂与胆固醇之间存在吸引相互作用。含有麦角固醇的混合物表现出截然不同的行为,即相互作用要么是排斥性的(与DPPC的混合物),要么体系是理想的(与DOPC的混合物)。所得结果对多烯抗生素的作用方式具有启示意义,即与胆固醇(哺乳动物细胞膜的主要甾醇)相比,多烯类可能更容易与真菌细胞中存在的麦角固醇相互作用。