含有可电离的阴离子脂质的膜的不稳定性:头组和尾结构的排斥范围的影响
Hao-Chun Huang1, Chih-Jung Lin2, Yu-Jane Sheng2
1Department of Chemical and Materials Engineering, National Central University, Jhongli 320, Taiwan.
Colloids and surfaces. B, Biointerfaces
|February 28, 2024
概括
在可电离的阴离子脂质中,膜稳定性对于脂质纳米颗粒内体逃脱至关重要,随着内体酸化导致的头组排斥增加而下降. 当静电排斥超过关键值时,膜完整性就会丧失,这取决于脂质尾结构.
科学领域:
- 生物物理学的生物物理.
- 材料科学 材料科学 材料科学
- 计算化学计算化学
背景情况:
- 可电离的阴离子脂质是脂质纳米颗粒 (LNP) 的关键组成部分,用于有效的内体逃生.
- 内体酸化触发了脂质电离,改变了膜的特性.
研究的目的:
- 在内体酸化条件下研究由可电离的阴离子脂质形成的膜的结构稳定性.
- 了解静电排斥和脂质尾结构对膜完整性的影响.
主要方法:
- 使用粗粒散射粒子动力学 (CG-DPD) 模拟.
- 将静电排斥作为一种具有远程切断 (rc,HH) 的保守力进行建模.
- 显而易见的加入和加强库伦比克排斥.
主要成果:
- 当静电排斥力 (通过rc,HH或明确的库伦力模拟) 超过临界值时,膜和囊泡的结构完整性就会丧失.
- 膜不稳定性取决于脂质尾部结构和电离脂质的分数.
- 在具有高电荷分数的混合脂质膜中观察到双层结构的破坏.
结论:
- 由于内体酸化而增加的静电排斥可以破坏可电离的阴性脂质膜的稳定.
- 脂质尾结构和充电分数显著影响膜的稳定性.
- 膜不稳定性与偏离单位的包装参数减少有关.
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