抗菌小蛋白當超過一個臨界濃度時,會誘發孔洞形成於脂膜中.將脂膜變質會導致臨界濃度的改變.例如,我們最近的報告顯示:在PC 脂膜中添加PE 脂質分子會提高臨界濃度.在這次的三年計畫中,我們將研究脂膜裡的膽固醇對抗菌小蛋白誘發孔洞形成於脂膜中的影響.計畫將進行四種實驗:指向性圓極化雙光譜; 片層X-光繞射;微細管微胞吸取;滴定圓極化雙光譜.計畫探討三類與抗菌小蛋白作用的脂質/膽固醇之脂膜系統:第一年,探討一種脂質分子與膽固醇的雙混合脂膜;第二年,探討一種未飽和脂質分子,一種飽和脂質分子與膽固醇的參混合脂膜; 第三年,探討一種未飽和脂質分子,sphingomyelin 與膽固醇的參混合脂膜.實驗結果有助於瞭解含有膽固醇的脯乳類細胞膜如何免於抗菌小蛋白的殺戮。 When exceeding a threshold concentration, antimicrobial peptides can induce pore formation in lipid membrane. Modifying the lipid membrane leads to the change of threshold concentration. For example, our recent report shows that adding PE lipid molecules into a PC lipid membrane leads to a higher threshold concentration (Lee et al. 2005). In this 3-year project, we will study the effect of membrane-containing cholesterols on peptide-induced pore formation. Four established experiments in our lab will be conducted: oriented circular dichroism, lamellar X-ray diffraction, vesicle micro-pipette aspiration and titration circular dichroism. Three membrane systems of lipid/cholesterol to interact with antimicrobial peptide will be investigated: 1. binary mixture of one lipid and cholesterol in first year; 2. ternary mixture of one saturated lipid, one unsaturated lipid and cholesterol in second year; 3. ternary mixture of one unsaturated lipid, sphingomyelin and cholesterol in third year. The result will help us to understand how mammalian cell membranes containing cholesterol can survive from the killing of antimicrobial peptides. 研究期間:9608 ~ 9707