Photodamage of lipid bilayers by irradiation of a fluorescently labeled cell-penetrating peptide.
Photodamage of lipid bilayers by irradiation of a fluorescently labeled cell-penetrating peptide.
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DOI：
10.1016/j.bbagen.2013.10.011
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发表时间：
2014-01
影响因子：
3
通讯作者：
Pellois, Jean-Philippe
中科院分区：
文献类型：
--
作者：
Meerovich, Igor;Muthukrishnan, Nandhini;Johnson, Gregory A.;Erazo-Oliveras, Alfredo;Pellois, Jean-Philippe
荧光标记的细胞穿透肽可以通过内吞作用移位到细胞中，并且在光照射下，溶解内吞囊泡。Fl-CPP的这种光诱导的内体溶解活性可用于有效地将大分子如蛋白质和核酸以及其他小有机分子递送到活细胞的胞质溶胶中。诱导光解的光触发的要求为细胞内递送过程提供了更多的空间和时间控制。在这份报告中，我们研究了分子水平的机制，细胞穿透肽，如达特时，用小的有机荧光分子标记获得光诱导的裂解活性，使用一个简化的模型的脂质囊泡。用5（6）-羧基-四甲基罗丹明标记的肽达特与带负电荷的磷脂结合，从而使荧光团靠近脂质体的膜。在光照射时，激发的荧光团在脂质双层处产生活性氧物质，并且实现膜的氧化。此外，荧光肽引起光氧化脂质的聚集，这是一种需要肽序列中存在精氨酸残基的活性。这些结果表明，细胞穿透肽起着双重作用。一方面，达特将缀合的荧光团靶向膜。另一方面，达特直接参与光敏化膜的去稳定化。因此，肽和荧光团似乎协同作用以有效地破坏膜。了解Fl-CPP介导的膜光损伤背后的机制将有助于设计最佳的光内体溶解化合物。
Fluorescently labeled cell-penetrating peptides can translocate into cells by endocytosis and upon light irradiation, lyse the endocytic vesicles. This photo-inducible endosomolytic activity of Fl-CPPs can be used to efficiently deliver macromolecules such as proteins and nucleic acids and other small organic molecules into the cytosol of live cells. The requirement of a light trigger to induce photolysis provides a more spatial and temporal control to the intracellular delivery process. In this report, we examine the molecular level mechanisms by which cell-penetrating peptides such as TAT when labeled with small organic fluorophore molecules acquire a photo-induced lytic activity using a simplified model of lipid vesicles. The peptide TAT labeled with 5(6)-carboxy-tetramethylrhodamine binds to negatively charged phospholipids, thereby bringing the fluorophore in close proximity to the membrane of liposomes. Upon light irradiation, the excited fluorophore produces reactive oxygen species at the lipid bilayer and oxidation of the membrane is achieved. In addition, the fluorescent peptide causes aggregation of photo-oxidized lipids, an activity that requires the presence of arginine residues in the peptide sequence. These results suggest that the cell penetrating peptide plays a dual role. On one hand, TAT targets a conjugated fluorophore to membranes. On the other hand, TAT participates directly in the destabilization of photosensitized membranes. Peptide and fluorophore therefore appear to act in synergy to destroy membranes efficiently. Understanding the mechanism behind Fl-CPP mediated membrane photodamage will help to design optimally photo-endosomolytic compounds.
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影响因子：
--
作者：
Choi, HS;Kim, JW;Kim, C
通讯作者：
Kim, C
影响因子：
3.3
作者：
GANDIN, E;LION, Y;VANDEVORST, A
通讯作者：
VANDEVORST, A
影响因子：
4.5
作者：
Chen B;Jiang Y;Zeng S;Yan J;Li X;Zhang Y;Zou W;Wang X
通讯作者：
Wang X
影响因子：
15
作者：
Maiolo, JR;Ottinger, EA;Ferrer, M
通讯作者：
Ferrer, M
影响因子：
3.3
作者：
GROSSWEINER, LI;PATEL, AS;GROSSWEINER, JB
通讯作者：
GROSSWEINER, JB