Effect of Nanoparticles on the Biochemical and Behavioral Aging Phenotype of the Nematode Caenorhabditis elegans

Abstract

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.

A real-time documentation and mechanistic investigation of quantum dots-induced autophagy in live Caenorhabditis elegans

“…In recent years, C. elegans has also gained increasing popularity among researchers to assess the in vivo toxicity of many different kinds of nanomaterials, including metal-based nanomaterials [40e42], carbon-based nanomaterials [43e47], fluorescent quantum dots [48e50], upconversion nanocrystals [51,52], and silica nanomaterials [53,54]. For examples, Choi and co-workers have shown that after exposure to silver nanoparticles, serious toxicity for the C. elegans is found, such as reproductive senescence and early death.…”

Pathology and function of nuclear amyloid

“…Examples are changes of thermal conditions as observed in heat shock responses or experimentally induced fluctuations. Consistently, several reports describe controlled nucleation of protein fibrillation by heat shock, metals, or nanoparticles in vitro, in mammalian cell culture as well as in whole organisms 10 , 22 - 25 . The analysis of intracellular amyloid formation has advanced in recent years due to the diagnostic value of amyloid fibril localization within cells and tissues 26 .…”

“…Amyloid-indicating features such as Congo red and Thioflavin T-binding as well as reactivity with amyloid-specific antibodies and peptides can be located in distinct subnuclear microenvironments under physiological conditions 18 , 24 , 25 . Moreover, 55% of eukaryotic proteins are predicted to contain unstructured protein regions that are intrinsically amyloidogenic 21 , 70 .…”

“…Consistent with these ideas is the notion that the nucleus represents a highly crowded environment which on one hand essentially enables the self-organization of macromolecular, multiprotein complexes, however, likewise potentially promotes aberrant amyloid protein fibrillation through inordinate volume exclusion 14 , 64 - 67 . Along these lines it was shown that xenobiotics such as certain heavy metals and nanoparticles sustain amyloid protein fibrillation, accumulate in specific nuclear microenvironments and locally induce nuclear amyloid 22 - 25 . Thus, a fine balance between nuclear crowding and overcrowding may be required to maintain functional protein aggregation.…”

Vitamin E ameliorates neurodegeneration related phenotypes caused by neurotoxicity of Al2O3-nanoparticles in C. elegans

“…58,59 Previous studies have also suggested that Al 2 O 3 -NPs could decrease the locomotion behavior of wild-type N2 nematodes. 32,33 In this study, we further indicate that exposure to Al 2 O 3 -NPs at concentrations in the range of mg L −1 could induce neurodegenerative related phenotypes in nematodes, such as the neurodegeneration in D-type GABAergic nervous system (Fig.…”