Antimicrobial peptide magainin 2 forms pores in lipid bilayers, a property that is considered the main cause of its bactericidal activity. Recent data suggest that tension or stretching of the inner monolayer plays an important role in magainin 2-induced pore formation in lipid bilayers. Here, to elucidate the mechanism of magainin 2-induced pore formation, we investigated the effect on pore formation of asymmetric lipid distribution in two monolayers. First, we developed a method to prepare giant unilamellar vesicles (GUVs) composed of dioleoylphosphatidylglycerol (DOPG), dioleoylphosphatidylcholine (DOPC), and lyso-PC (LPC) in the inner monolayer and of DOPG/DOPC in the outer monolayer. We consider that in these GUVs, the lipid packing in the inner monolayer was larger than that in the outer monolayer. Next, we investigated the interaction of magainin 2 with these GUVs with an asymmetric distribution of LPC using the single GUV method, and found that the rate constant of magainin 2-induced pore formation, k_p, decreased with increasing LPC concentration in the inner monolayer. We constructed a quantitative model of magainin 2-induced pore formation, whereby the binding of magainin 2 to the outer monolayer of a GUV induces stretching of the inner monolayer, causing pore formation. A theoretical equation defining k_p as a function of magainin 2 surface concentration, X, reasonably explains the experimental relationship between k_p and X. This model quantitatively explains the effect on k_p of the LPC concentration in the inner monolayer. On the basis of these results, we discuss the mechanism of the initial stage of magainin 2-induced pore formation.

中文翻译：

---

抗菌肽Magainin 2诱导毛孔形成初期的机理

抗菌肽magainin 2在脂质双层中形成孔，该特性被认为是其杀菌活性的主要原因。最近的数据表明，内部单层细胞的拉伸或拉伸在magainin 2诱导的脂质双分子层中的孔形成中起着重要作用。在这里，为了阐明由magainin 2诱导的孔形成的机制，我们调查了两个单层中不对称脂质分布对孔形成的影响。首先，我们开发了一种方法，用于制备内部单层中由二油酰基磷脂酰甘油（DOPG），二油酰基磷脂酰胆碱（DOPC）和溶血PC（LPC）组成的单层大囊泡（GUV），以及在外单层中制备DOPG / DOPC的溶血PC（LPC）。我们认为在这些GUV中，内部单层中的脂质堆积大于外部单层中的脂质堆积。下一个，k _p，随着内部单层中LPC浓度的增加而降低。我们构建了由洋红蛋白2诱导的孔形成的定量模型，其中洋红蛋白2与GUV的外单层的结合诱导了内单层的拉伸，从而导致了孔的形成。将k _p定义为magainin 2表面浓度X的函数的理论方程式合理地解释了k _p和X之间的实验关系。该模型定量解释了内部单层中LPC浓度对k _p的影响。基于这些结果，我们讨论了由magainin 2诱导的孔形成的初始阶段的机制。