Effect of hydrophobic moment on membrane interaction and cell penetration of apolipoprotein E-derived arginine-rich amphipathic α-helical peptides.
Effect of hydrophobic moment on membrane interaction and cell penetration of apolipoprotein E-derived arginine-rich amphipathic α-helical peptides.
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DOI：
10.1038/s41598-022-08876-9
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发表时间：
2022-03-23
影响因子：
4.6
通讯作者：
Saito H
中科院分区：
文献类型：
--
作者：
Takechi-Haraya Y;Ohgita T;Kotani M;Kono H;Saito C;Tamagaki-Asahina H;Nishitsuji K;Uchimura K;Sato T;Kawano R;Sakai-Kato K;Izutsu KI;Saito H
我们先前开发了一种两亲性的富含精氨酸的肽A2-17，其具有直接穿透细胞膜的高能力。为了理解A2-17肽的有效细胞穿透能力的机制，我们设计了具有不同疏水矩值的A2-17的三种结构异构体，并比较了它们的膜相互作用和直接细胞穿透。共聚焦荧光显微镜显示肽的细胞穿透效率倾向于随着其疏水性矩的增加而增加，其中具有最高疏水性矩的A2 -17异构体A2 -17 L14 R/R15 L主要保留在浆细胞膜上。同时，Trp荧光分析表明，在所有A2-17异构体中，A2-17 L14 R/R15 L插入脂质膜最深。电生理分析表明，A2-17 L14 R/R15 L的肽诱导的脂质膜孔的持续时间和电荷通量是突出的，表明稳定的膜孔的形成。事实上，A2-17 L14 R/R15 L肽对CHO-K1细胞表现出最强的膜损伤。原子力显微镜定量定义的肽诱导的膜扰动的刚度的脂质囊泡，这与所有A2-17异构体的疏水性时刻的减少。这些结果表明，两亲性A2-17肽的最佳膜扰动对于其有效渗透到细胞中而不诱导稳定的膜孔是至关重要的。
We previously developed an amphipathic arginine-rich peptide, A2-17, which has high ability to directly penetrate across cell membranes. To understand the mechanism of the efficient cell-penetrating ability of the A2-17 peptide, we designed three structural isomers of A2-17 having different values of the hydrophobic moment and compared their membrane interaction and direct cell penetration. Confocal fluorescence microscopy revealed that cell penetration efficiency of peptides tends to increase with their hydrophobic moment, in which A2-17 L14R/R15L, an A2-17 isomer with the highest hydrophobic moment, predominantly remains on plasma cell membranes. Consistently, Trp fluorescence analysis indicated the deepest insertion of A2-17 L14R/R15L into lipid membranes among all A2-17 isomers. Electrophysiological analysis showed that the duration and charge flux of peptide-induced pores in lipid membranes were prominent for A2-17 L14R/R15L, indicating the formation of stable membrane pores. Indeed, the A2-17 L14R/R15L peptide exhibited the strongest membrane damage to CHO-K1 cells. Atomic force microscopy quantitatively defined the peptide-induced membrane perturbation as the decrease in the stiffness of lipid vesicles, which was correlated with the hydrophobic moment of all A2-17 isomers. These results indicate that optimal membrane perturbation by amphipathic A2-17 peptide is critical for its efficient penetration into cells without inducing stabilized membrane pores.
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DOI：
10.1002/anie.201801361
发表时间：
2018-09-10
期刊：
Angewandte Chemie (International ed. in English)
影响因子：
--
作者：
Peraro L;Kritzer JA
通讯作者：
Kritzer JA
影响因子：
1.6
作者：
HUTTER, JL;BECHHOEFER, J
通讯作者：
BECHHOEFER, J
影响因子：
2.9
作者：
Ladokhin, AS;Jayasinghe, S;White, SH
通讯作者：
White, SH
DOI：
10.3390/molecules22111929
发表时间：
2017-11-08
期刊：
Molecules (Basel, Switzerland)
影响因子：
--
作者：
Kalafatovic D;Giralt E
通讯作者：
Giralt E
影响因子：
3.4
作者：
Bahnsen, Jesper Soborg;Franzyk, Henrik;Nielsen, Hanne Morck
通讯作者：
Nielsen, Hanne Morck