霍克斯特33342与不同pH值的POPC膜的相互作用
Margarida M Cordeiro1,2, Hugo A L Filipe1,3, Patrícia Dos Santos1,2
1Coimbra Chemistry Center, Institute of Molecular Sciences (CQC-IMS), University of Coimbra, 3004-535 Coimbra, Portugal.
Molecules (Basel, Switzerland)
|August 12, 2023
概括
霍克斯特33342 (H33342) 膜关联显示了最小的pH值依赖的变化. 这种光探测器有效地分成脂质双层,带电的形式由于结合而表现出显著的脂友性.
科学领域:
- 生物物理学的生物物理.
- 细胞生物学 细胞生物学
- 计算化学计算化学
背景情况:
- 霍克斯特33342 (H33342) 是一种重要的光探针,用于染色活细胞中的DNA.
- H33342必须穿透细胞膜,在生理pH值下具有充电,这给人带来了挑战.
- 了解pH对H33342-膜相互作用的影响对于精确的细胞成像至关重要.
研究的目的:
- 为了研究pH值对Hoechst 33342 (H33342) 与脂质双层的关联的影响.
- 量化H33342在相关的pH范围 (5-10) 的分割系数.
- 阐明控制H33342-膜相互作用的分子机制.
主要方法:
- 使用光光谱学和异热定位热量计 (ITC) 的实验量化.
- 计算建模包括对同位素稳定性的量子化学计算.
- 分子动力学 (MD) 模拟 (无约束和采样) 用于研究同位素-双层相互作用.
主要成果:
- 在广泛的pH范围内,H33342的分离系数变化极小 (不到一个数量级).
- 凝聚力分析表明H33342和POPC脂质之间存在强烈的结,特别是+2充电形式.
- MD模拟证实了结,并揭示了充电H33342物种的高脂友性.
结论:
- H33342在广泛的pH频谱中表现出强大的膜协会,这对其作为活细胞成像探针的功能至关重要.
- 结对充电的H33342的脂性有显著的贡献,影响其膜亲和力.
- 将脂性与疏水性区分开来,是预测生物膜中的探针行为的关键.
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