IUF-Leibniz Research Institute for Environmental Medicine, Heinrich-Heine-University Duesseldorf , Auf'm Hennekamp 50, 40225 Düsseldorf, Germany.
ACS Nano. 2013 Dec 23;7(12):10695-703. doi: 10.1021/nn403443r. Epub 2013 Nov 23.
Invertebrate animal models such as the nematode Caenorhabditis elegans (C. elegans) are increasingly used in nanotechnological applications. Research in this area covers a wide range from remote control of worm behavior by nanoparticles (NPs) to evaluation of organismal nanomaterial safety. Despite of the broad spectrum of investigated NP-bio interactions, little is known about the role of nanomaterials with respect to aging processes in C. elegans. We trace NPs in single cells of adult C. elegans and correlate particle distribution with the worm's metabolism and organ function. By confocal microscopy analysis of fluorescently labeled NPs in living worms, we identify two entry portals for the uptake of nanomaterials via the pharynx to the intestinal system and via the vulva to the reproductive system. NPs are localized throughout the cytoplasm and the cell nucleus in single intestinal, and vulval B and D cells. Silica NPs induce an untimely accumulation of insoluble ubiquitinated proteins, nuclear amyloid and reduction of pharyngeal pumping that taken together constitute a premature aging phenotype of C. elegans on the molecular and behavioral level, respectively. Screening of different nanomaterials for their effects on protein solubility shows that polystyrene or silver NPs do not induce accumulation of ubiquitinated proteins suggesting that alteration of protein homeostasis is a unique property of silica NPs. The nematode C. elegans represents an excellent model to investigate the effect of different types of nanomaterials on aging at the molecule, cell, and whole organism level.
无脊椎动物模型，如秀丽隐杆线虫（C. elegans），越来越多地被应用于纳米技术领域。该领域的研究涵盖了从纳米粒子（NPs）远程控制蠕虫行为到评估生物体纳米材料安全性的广泛范围。尽管研究了 NP-生物相互作用的广泛谱，但对于纳米材料在 C. elegans 衰老过程中的作用知之甚少。我们在成年 C. elegans 的单个细胞中追踪 NPs，并将颗粒分布与蠕虫的新陈代谢和器官功能相关联。通过对活体蠕虫中荧光标记 NPs 的共聚焦显微镜分析，我们确定了纳米材料通过咽进入肠道系统和通过阴道进入生殖系统的两种摄取途径。NPs 在单个肠道细胞和阴道 B 和 D 细胞的细胞质和细胞核中均有定位。二氧化硅 NPs 会导致不可溶的泛素化蛋白、核淀粉样蛋白的过早积累以及咽泵吸的减少，这些共同构成了 C. elegans 在分子和行为水平上的过早衰老表型。对不同纳米材料对蛋白质溶解度影响的筛选表明，聚苯乙烯或银 NPs 不会诱导泛素化蛋白的积累，这表明蛋白质平衡的改变是二氧化硅 NPs 的独特特性。秀丽隐杆线虫是研究不同类型的纳米材料对分子、细胞和整个生物体衰老影响的极好模型。
