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Nanomolar LL-37 induces permeability of a biomimetic mitochondrial membrane
Nanoscale ( IF 6.7 ) Pub Date : 2022-11-16 , DOI: 10.1039/d2nr05409d
Xin Jiang 1 , Chenguang Yang 2, 3 , Jie Qiu 1 , Dongfei Ma 1 , Cheng Xu 1, 4 , Shuxin Hu 2, 3 , Weijing Han 1 , Bing Yuan 1 , Ying Lu 2, 3
Affiliation  

LL-37, the only human host cathelicidin peptide, is proposed to be able to induce host cell apoptosis through mitochondrial membrane permeabilization (MMP). Detailed pathways of the LL-37-triggered MMP are however still disputed. It is generally believed that cationic peptides permeate a membrane mostly in conditions of micromolar peptide concentrations and negatively charged membranes, which are not usually satisfied in the mitochondrial circumstance. Herein, using a variety of single-molecule techniques, we show that nanomolar LL-37 specifically induces permeability of a phosphoethanolamine (PE)-rich biomimetic mitochondrial membrane in a protein-independent manner. The insertion dynamics of single LL-37 molecules exhibit different metastable states in bilayers composed of different lipids. Moreover, the PE lipids significantly facilitate adsorption and accumulation of LL-37 on the PE-rich bilayer, and produce deeper insertion of peptide oligomers, especially tetramers, into the bilayer. This work offers an alternative pathway of the LL-37-triggered MMP and apoptosis.

中文翻译:

纳摩尔 LL-37 诱导仿生线粒体膜的通透性

LL-37 是唯一的人类宿主导管素肽,被认为能够通过线粒体膜透化 (MMP) 诱导宿主细胞凋亡。然而,LL-37 触发的 MMP 的详细途径仍然存在争议。一般认为,阳离子肽主要在微摩尔肽浓度和带负电荷的膜条件下渗透膜,而线粒体环境通常不能满足这些条件。在此,我们使用多种单分子技术表明,纳摩尔 LL-37 以不依赖于蛋白质的方式特异性诱导富含磷酸乙醇胺 (PE) 的仿生线粒体膜的通透性。单个 LL-37 分子的插入动力学在由不同脂质组成的双层中表现出不同的亚稳态。而且,PE 脂质显着促进了 LL-37 在富含 PE 的双层上的吸附和积累,并使肽寡聚体(尤其是四聚体)更深地插入到双层中。这项工作提供了 LL-37 触发的 MMP 和细胞凋亡的替代途径。
更新日期:2022-11-16
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