In Situ Modification of Plain Liposomes with Lipidated Coiled Coil Forming Peptides Induces Membrane Fusion
In Situ Modification of Plain Liposomes with Lipidated Coiled Coil Forming Peptides Induces Membrane Fusion
复制标题
DOI：
10.1021/ja4031227
复制
发表时间：
2013-05-29
影响因子：
15
通讯作者：
Kros, Alexander
中科院分区：
文献类型：
--
作者：
Versluis, Frank;Voskuhl, Jens;Kros, Alexander
嵌入脂质体膜中的互补卷曲螺旋形成脂化肽能够诱导快速、受控和靶向的膜融合。传统上，这样的融合脂质体通过在有机溶剂（例如，氯仿）中混合脂质和脂化肽来制备。在这里，我们原位制备了融合脂质体，即通过向普通脂质体中加入脂化肽溶液。由于脂质锚对于脂质体肽正确插入脂质体膜至关重要，因此设计了脂质化卷曲螺旋形成肽的小型文库，其中脂质结构是变化的。使用脂质和内容物混合测定筛选融合性，显示胆固醇修饰的卷曲螺旋肽诱导最有效的膜融合。重要的是，脂质和内容物混合实验都表明，用胆固醇修饰的肽对普通脂质体进行原位修饰产生高度融合的脂质体。这项工作表明，现有的膜可以用脂质化的卷曲螺旋形成肽激活，这可能导致高度有效的应用，如脂质体与细胞的融合。
Complementary coiled coil forming lipidated peptides embedded in liposomal membranes are able to induce rapid, controlled, and targeted membrane fusion. Traditionally, such fusogenic liposomes are prepared by mixing lipids and lipidated peptides in organic solvent (e g, chloroform). Here we prepared fusogenic liposomes in situ, i.e, by addition of a lipidated peptide solution to plain liposomes. As the lipid anchor is vital for the correct insertion of lipidatecl peptides into liposomal membranes, a small library of lipidated coiled coil forming peptides was designed in which the lipid structure was varied. The fusogenicity was screened using lipid and content mixing assays showing that cholesterol modified coiled coil peptides induced the most efficient fusion of membranes. Importantly, both lipid and content mixing experiments demonstrated that the in situ modification of plain liposomes with the cholesterol modified peptides yielded highly fusogenic liposomes. This work shows that existing membranes can be activated with lipidated coiled coil forming peptides, which might lead to highly potent applications such as the fusion of liposomes with cells.