Penetration of Lipid Membranes by Gold Nanoparticles: Insights into Cellular Uptake, Cytotoxicity, and Their Relationship
Penetration of Lipid Membranes by Gold Nanoparticles: Insights into Cellular Uptake, Cytotoxicity, and Their Relationship
复制标题
金纳米粒子穿透脂质膜：深入了解细胞摄取、细胞毒性及其关系
DOI：
10.1021/nn1010792
复制
发表时间：
2010-09-01
期刊：
影响因子：
17.1
通讯作者：
Zheng, Yonggang
中科院分区：
文献类型：
--
作者：
Lin, Jiaqi;Zhang, Hongwu;Zheng, Yonggang
纳米颗粒渗透到细胞膜中是一个有趣的现象，可能对纳米颗粒的生物医学应用具有重要意义。在本文中，金纳米粒子（AuNPs）的粗粒度模型开发（验证现有的实验数据），以模拟其与模型脂质膜的相互作用。模拟结果表明，金纳米粒子具有不同的迹象和密度的表面电荷自发地粘附到双层表面或渗透到双层内部。平均力计算的潜力表明，粘附或穿透时的能量增益是显着的。在渗透的情况下，它被发现，有缺陷的地区被诱导跨整个表面的双层的上小叶和一个亲水性的孔，运输水分子形成与其周围的脂质高度无序。渗透及其伴随的膜破坏可能是实验中观察到的两种现象的可能机制：AuNPs在内化到细胞中期间绕过内吞作用和AuNPs的细胞毒性。还发现，渗透和膜破坏的水平随着AuNP的电荷密度的增加而增加，但以不同的方式。这些发现提出了一种通过操纵AuNP的表面电荷密度来控制AuNP-细胞相互作用的方法，以实现其生物医学应用中的指定目标，例如在其细胞摄取和细胞毒性之间取得平衡，以实现作为递送剂的最佳递送效率。
Nanoparticle penetration into cell membranes is an interesting phenomenon that may have crucial implications on the nanoparticles' biomedical applications. In this paper, a coarse-grained model for gold nanoparticles (AuNPs) is developed (verified against experimental data available) to simulate their interactions with model lipid membranes. Simulations reveal that AuNPs with different signs and densities of surface charges spontaneously adhere to the bilayer surface or penetrate into the bilayer interior. The potential of mean force calculations show that the energy gains upon adhesion or penetration is significant. In the case of penetration, it is found that defective areas are induced across the entire surface of the upper leaflet of the bilayer and a hydrophilic pore that transports water molecules was formed with its surrounding lipids highly disordered. Penetration and its concomitant membrane disruptions can be a possible mechanism of the two observed phenomena in experiments: AuNPs bypass endocytosis during their internalization into cells and cytotoxicity of AuNPs. It is also found that both the level of penetration and membrane disruption increase as the charge density of the AuNP increases, but in different manners. The findings suggest a way of controlling the AuNP-cell interactions by manipulating surface charge densities of AuNPs to achieve designated goals in their biomedical applications, such as striking a balance between their cellular uptake and cytotoxicity in order to achieve optimal delivery efficiency as delivery agents.