Martin-Luther-Universität Halle-Wittenberg , 06099 Halle (Saale), Germany.
Department of Interface Chemistry and Surface Engineering , Max-Planck-Institut für Eisenforschung GmbH , 40237 Düsseldorf , Germany.
Langmuir. 2019 Apr 23;35(16):5501-5508. doi: 10.1021/acs.langmuir.8b04195. Epub 2019 Apr 10.
Liposomal membrane fusion is an important tool to study complex biological fusion mechanisms. We use lipidated derivatives of the specific heterodimeric coiled coil pair E: (EIAALEK) and K: (KIAALKE) to study and control the fusion of liposomes. In this model system, peptides are tethered to their liposomes via a poly(ethylene glycol) (PEG) spacer and a lipid anchor. The efficiency of the fusion mechanism and function of the peptides is highly affected by the PEG-spacer length and the lipid anchor type. Here, the influence of membrane-fusogen distance on the peptide-membrane interactions and the peptide secondary structures is studied with Langmuir film balance and infrared reflection absorption spectroscopy. We found that the introduction of a spacer to monolayer-tethered peptide E changes its conformation from solvated random coils to homo-oligomers. In contrast, the described peptide-monolayer interaction of peptide K is not affected by the PEG-spacer length. Furthermore, the coexistence of different conformations when both lipopeptides E and K are present at the membrane surface is demonstrated empirically, which has many implications for the design of effective fusogenic recognition units and the field of artificial membrane fusion.
脂质体膜融合是研究复杂生物融合机制的重要工具。我们使用特定异二聚体卷曲螺旋对 E（EIAALEK）和 K（KIAALKE）的脂质衍生物来研究和控制脂质体的融合。在这个模型系统中，肽通过聚乙二醇（PEG）间隔物和脂质锚定连接到它们的脂质体上。融合机制的效率和肽的功能受到 PEG 间隔物长度和脂质锚定类型的高度影响。在这里，我们使用 Langmuir 膜天平（Langmuir film balance）和红外反射吸收光谱（infrared reflection absorption spectroscopy）研究了膜融合剂距离对肽-膜相互作用和肽二级结构的影响。我们发现，引入间隔物会使单层键合的肽 E 从溶剂化的无规卷曲转变为同聚体寡聚物。相比之下，描述的肽 K 的肽-单层相互作用不受 PEG 间隔物长度的影响。此外，还通过实验证明了当两种脂肽 E 和 K 同时存在于膜表面时存在不同构象的共存，这对有效融合识别单元的设计和人工膜融合领域具有重要意义。
