Université de Lyon, Villeurbanne, F-69622, France.
Langmuir. 2011 Sep 6;27(17):10785-92. doi: 10.1021/la200767e. Epub 2011 Jul 28.
Mycosubtilin is a natural antimicrobial lipopeptide produced by Bacillus subtilis strains. It is characterized by its hemolytic and strong antifungal activities. Mycosubtilin interacts with the plasma membranes of sensitive cells. However, the molecular mechanisms of its biological activities have not been completely elucidated. Our purpose was therefore to analyze the interactions of mycosubtilin with biological membranes by using biomimetic membranes such as Langmuir monolayers and multilayers. Structural changes of mycosubtilin, involving its peptide backbone and the side chain of its tyrosyl residue, were observed when the lipopeptide was interacting with cholesterol-containing multilayers. The interactions of mycosubtilin with monolayers constituted by pure lipids and by phosholipid/cholesterol or phospholipid/sphingomyelin/cholesterol were also examined. An original behavior of mycosubtilin toward cholesterol-containing monolayers was found. However, this original behavior was lost when mycosubtilin was interacting with pure cholesterylacetate monolayers. This suggests the involvement of the alcohol group of cholesterol in mycosubtilin-cholesterol interactions within membranes. Moreover, mycosubtilin induced changes in the organization and morphology of cholesterol-containing monolayers, and large condensed domains with different levels of condensation appeared only in the case of DPPC/sphingomyelin/cholesterol monolayer.
抑菌肽是枯草芽孢杆菌产生的一种天然抗菌脂肽。它的特点是具有溶血活性和较强的抗真菌活性。抑菌肽与敏感细胞的质膜相互作用。然而，其生物活性的分子机制尚未完全阐明。因此，我们的目的是通过使用类脂膜如 Langmuir 单层膜和多层膜来分析抑菌肽与生物膜的相互作用。当脂肽与含有胆固醇的多层膜相互作用时，观察到抑菌肽的结构变化，涉及肽骨架和其酪氨酸残基的侧链。还研究了抑菌肽与由纯脂、磷脂/胆固醇或磷脂/鞘磷脂/胆固醇组成的单层膜的相互作用。发现抑菌肽与含有胆固醇的单层膜具有独特的相互作用行为。然而，当抑菌肽与纯胆甾醇乙酸酯单层膜相互作用时，这种独特的行为消失了。这表明胆固醇的醇基团参与了抑菌肽与膜内胆固醇的相互作用。此外，抑菌肽诱导含有胆固醇的单层膜的组织和形态发生变化，并且仅在 DPPC/鞘磷脂/胆固醇单层膜的情况下出现具有不同程度凝聚的大凝聚域。
