Filipin Orientation Revealed by Linear Dichroism. Implication for a Model of Action

详细信息    查看全文

• 作者：Sí ; lvia C. D. N. Lopes ; Erik Goormaghtigh ; Benedito J. Costa Cabral ; and Miguel A. R. B. Castanho
• 刊名：Journal of the American Chemical Society
• 出版年：2004
• 出版时间：May 5, 2004
• 年：2004
• 卷：126
• 期：17
• 页码：5396 - 5402
• 全文大小：164K
• 年卷期：v.126,no.17(May 5, 2004)
• ISSN：1520-5126

文摘

The organization of the polyene antibiotic filipin in membranes containing cholesterol is acontroversial matter of debate. Two contradictory models exist, one suggesting a parallel and the otherperpendicular organization of filipin with respect to the plane of the membrane. UV-vis linear dichroism,ATR-FTIR, and fluorescence anisotropy decay techniques were combined to study the orientation of filipinin model systems of membranes composed of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC)or 1,2-palmitoyl-sn-glycero-3-phosphocholine (DPPC) with and without cholesterol. Filipin's orientation isdetermined by the presence/absence of cholesterol when it is inserted in gel crystalline phase modelmembranes. When cholesterol (33%) is present in DPPC bilayers, filipin stands perpendicular to themembrane surface as expected in "pore-forming" models. At variance, absence of cholesterol leaves filipinin an essentially random organization in the lipidic matrix. In liquid crystalline phase bilayers (POPC) filipin'sorientation is perpendicular to the membrane surface even in absence of cholesterol. Thus filipin's activity/organization depends not only on cholesterol presence but also in the lipid phase domain it is inserted in.These findings were combined with spectroscopy and microscopy data in the literature, solving controversialmatters of debate.