Gold nanoparticles disrupt actin organization and pulmonary endothelial barriers
Gold nanoparticles disrupt actin organization and pulmonary endothelial barriers
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DOI：
10.1038/s41598-020-70148-1
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发表时间：
2020-08-07
影响因子：
4.6
通讯作者：
Leckband, Deborah E.
中科院分区：
文献类型：
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作者：
Sinclair, Whitney E.;Chang, Huei-Huei;Leckband, Deborah E.
本研究探讨了金纳米颗粒对人肺内皮细胞单分子层代谢活性和形态的影响。我们开发了三种不同尺寸和两种表面化学性质的金纳米粒子库，包括阴离子柠檬酸盐和阳离子聚电解质聚丙烯胺盐酸盐。纳米颗粒在细胞培养基中进行表征，以评估其物理性质在暴露于生物液体后如何改变。建立了牛血清白蛋白预处理方案，以稳定细胞培养基中的纳米颗粒。本研究结果表明，人肺动脉内皮细胞暴露于不同纳米颗粒18小时，对细胞代谢活性有轻微影响。然而，纳米颗粒暴露会扰乱皮层肌动蛋白网络并诱导细胞间隙的形成。特别是，暴露于聚丙烯胺盐酸盐包被的颗粒会减少细胞-细胞连接的面积，这种变化与内皮屏障的渗漏增加有关。聚丙烯胺包被纳米颗粒的上清液中过量的聚电解质封盖剂的存在显著影响内皮形态。用牛血清白蛋白预处理颗粒上清可减轻游离或结合的多电解质对内皮细胞单层的负面影响。
This study explored the impact of gold nanoparticles on the metabolic activity and morphology of human pulmonary endothelial cell monolayers. We developed a gold nanoparticle library of three different sizes and two surface chemistries that include anionic citrate and the cationic polyelectrolyte poly(allylamine hydrochloride). The nanoparticles were characterized in cell culture medium to assess how their physical properties are altered after exposure to biological fluids. A bovine serum albumin pretreatment protocol was developed to stabilize the nanoparticles in cell culture medium. Results of this study show that an 18 h exposure of human pulmonary artery endothelial cells to the different nanoparticles modestly affects cellular metabolic activity. However, nanoparticle exposure perturbs the cortical actin networks and induces the formation of intercellular gaps. In particular, exposure to the poly(allylamine hydrochloride)-coated particles reduces the area of cell-cell junctions-a change that correlates with increased leakiness of endothelial barriers. The presence of excess polyelectrolyte capping agents in the supernatant of poly(allylamine hydrochloride)-coated nanoparticles significantly impacts endothelial morphology. Pretreatment of the particle supernatant with bovine serum albumin mitigates the negative effects of free or bound polyelectrolytes on endothelial cell monolayers.