Loosening of Lipid Packing Promotes Oligoarginine Entry into Cells
Loosening of Lipid Packing Promotes Oligoarginine Entry into Cells
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DOI：
10.1002/anie.201703578
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发表时间：
2017-06-19
影响因子：
16.6
通讯作者：
Futaki, Shiroh
中科院分区：
文献类型：
--
作者：
Murayama, Tomo;Masuda, Toshihiro;Futaki, Shiroh
尽管广泛使用富含精氨酸的细胞穿透肽（CPP）-包括八精氨酸（R8）-作为细胞内递送载体，但其内化机制仍在争论中。使用极性敏感染料（二-4-ANEPPDHQ），其特征在于在活细胞膜中的脂质包装，并在广义极化方面进行评价。用膜弯曲诱导肽处理导致脂质包装的显著松动，从而导致增强的R8渗透。芘丁酸盐（PyB）是一种疏水性的反阴离子，可以促进R8膜的转位。有趣的是，PyB也积极诱导膜曲率和扰动脂质包装。已知R8在升高的浓度下直接穿过细胞膜。R8流入的网站被发现有松散的脂质包装比周围地区。脂质包裹松散被认为是控制CPP膜移位的关键因素。
Despite extensive use of arginine-rich cell-penetrating peptides (CPPs)-including octaarginine (R8)-as intracellular delivery vectors, mechanisms for their internalization are still under debate. Lipid packing in live cell membranes was characterized using a polarity-sensitive dye (di-4-ANEPPDHQ), and evaluated in terms of generalized polarization. Treatment with membrane curvature-inducing peptides led to significant loosening of the lipid packing, resulting in an enhanced R8 penetration. Pyrenebutyrate (PyB) is known to facilitate R8 membrane translocation by working as a hydrophobic counteranion. Interestingly, PyB also actively induced membrane curvature and perturbed lipid packing. R8 is known to directly cross cell membranes at elevated concentrations. The sites of R8 influx were found to have looser lipid packing than surrounding areas. Lipid packing loosening is proposed as a key factor that governs the membrane translocation of CPPs.