CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety , Institute of High Energy Physics, Chinese Academy of Sciences, and CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China , Beijing 100049 , China.
University of Chinese Academy of Sciences , Beijing 100049 , China.
ACS Nano. 2019 Aug 27;13(8):8680-8693. doi: 10.1021/acsnano.9b00114. Epub 2019 Jul 26.
When nanoparticles interact with cellular or organelle membranes, the coating ligands are known to affect the integrity of the membranes, which regulate cell death and inflammation. However, the molecular mechanisms of this modulation remain unresolved. Here, we use synchrotron X-ray liquid surface scattering and molecular dynamics simulations to study interface structures between phospholipids and gold nanorods (AuNRs) coated by surfactant and polyelectrolyte. These ligands are two types of widely used surface modification with different self-assembled structures and stabilities on the surface of nanoparticles. We reveal distinct mechanisms of the ligand stability in disrupting membrane integrity. We find that the cationic surfactant ligand cetyltrimethylammonium bromide detaches from the AuNRs and inserts into phospholipids, resulting in reduced membrane thickness by compressing the phospholipids to align with the shorter ligand. Conversely, the cationic polyelectrolyte ligand poly(diallyldimethylammonium chloride) is more stable on AuNRs; although it adsorbs onto the membrane, it does not cause much impairment. The distinct coating ligand interactions with phospholipids are further verified by cellular responses including impaired lysosomal membranes and triggered inflammatory effects in macrophages. Together, the quantitative analysis of interface structures elucidates key bio-nano interactions and highlights the importance of surface ligand stability for safety and rational design of nanoparticles.
当纳米粒子与细胞膜或细胞器膜相互作用时，已知涂层配体影响膜的完整性，而膜完整性又调节细胞死亡和炎症。然而，这种调节的分子机制仍未解决。在这里，我们使用同步加速器 X 射线液体表面散射和分子动力学模拟来研究表面活性剂和聚电解质包覆的金纳米棒（AuNRs）与磷脂之间的界面结构。这两种配体是两种广泛使用的表面改性剂，它们在纳米粒子表面的自组装结构和稳定性不同。我们揭示了配体稳定性在破坏膜完整性方面的不同机制。我们发现，阳离子表面活性剂配体十六烷基三甲基溴化铵从 AuNRs 上脱离并插入磷脂中，通过压缩磷脂使其与较短的配体对齐，从而减少膜的厚度。相反，阳离子聚电解质配体聚二烯丙基二甲基氯化铵在 AuNRs 上更稳定；尽管它吸附在膜上，但不会造成太大的损伤。通过包括溶酶体膜损伤和巨噬细胞中触发炎症反应在内的细胞反应，进一步验证了不同的涂层配体与磷脂的相互作用。界面结构的定量分析阐明了关键的生物-纳米相互作用，并强调了表面配体稳定性对于纳米粒子的安全性和合理设计的重要性。
