阿波利波蛋白E衍生的氨酸丰富的结构灵活性提高了它们的细胞透能力
Yuki Takechi-Haraya1, Takashi Ohgita2, Akiko Usui3
1Division of Drugs, National Institute of Health Sciences, 3-25-26 Tonomachi, Kawasaki-ku, Kawasaki, 210-9501, Japan. haraya@nihs.go.jp.
Scientific reports
|November 8, 2023
概括
A2-17的结构灵活性增强了它的细胞膜透. 为了了解膜相互作用机制,研究了这种两性及其受约束类型.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 生物物理学的生物物理.
背景情况:
- 富含氨酸的两性因其膜相互作用特性而引起人们的兴趣.
- 与其同位素相比,A2-17具有较高的细胞透率.
- 了解-膜相互作用的机制对于药物输送和生物材料至关重要.
研究的目的:
- 为了研究A2-17的直接细胞膜透机制.
- 阐明结构灵活性在酸诱导的膜扰动和细胞进入中的作用.
- 为了比较A2-17的膜相互作用和细胞透与结构受约束的类似物.
主要方法:
- 设计和合成形状受约束的类似物:合 (StpA2-17) 和合 (StchA2-17) .
- 循环二重化谱法用于评估二次结构.
- 同焦显微镜用于细胞透效率.
- 托芬光用于膜插入深度.
- 原子力显微镜用于脂质体机械刚性.
- 平面脂质双层对孔形成的电生理学分析.
主要成果:
- A2-17,但不是它的类似物,在脂质体结合时表现出线圈到螺旋转变.
- 与StpA2-17相比,A2-17表现出更高的细胞透效率;StchA2-17没有透细胞.
- 与类似物相比,A2-17显著降低了脂质体的机械刚性,并诱导了通过短暂孔的更大的电荷流入.
- 所有都显示出类似的膜插入深度,但StchA2-17具有更高的膜亲和力.
结论:
- A2-17的结构灵活性对于其穿透细胞膜至关重要.
- 采用多样化的形状的能力促进了膜扰动模式,促进了细胞进入.
- 形状约束阻碍了A2-17的膜扰动和细胞透能力.
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