Silica nanoparticles disrupt OPT-2/PEP-2-dependent trafficking of nutrient peptides in the intestinal epithelium

Abstract

Despite of the increasing application of silica nanoparticles and identification of oral exposure as a major entry portal, we lack understanding of nanosilica effects in the gut. Thus, we investigated biointeractions of nanosilica with single intestinal cells. The invertebrate nematode Caenorhabditis elegans was chosen as model organism with a tractable intestine and realistic target organism of nanomaterials in the environment. We found that nanosilica impairs the intestinal uptake of oligopeptides. Downstream to absorption by the apical OPT-2/PEP-2 transporter dipeptides were trapped in aberrant vesicles that grow over time and reach diameters of !6 lm. The peptide vesicles do not correspond to known organelles such as gut granules and form independently of related gene products GLO-1 or GLO-3. Formation of aberrant peptide vesicles also occurred independently of insulin/IGF-I receptor (DAF-2) signaling and daf-2 loss of function mutants showed specific vesicle patterns including distinct localization along the apical membrane of single intestinal cells. As malnutrition of exposed C. elegans manifested in reduced growth and a petite phenotype similar to OPT-2/PEP-2 transporter deficient mutants, we conclude that nanosilica-induced peptide vesicles represent a new compartment of di-and tripeptide trapping which disrupts hydrolysis of nutrient peptides and metabolism.

Comprehensive phenotyping and transcriptome profiling to study nanotoxicity inC. elegans

“…Further study is required to elucidate the answer to this question. It was shown that co-feeding nanoparticles with E. coli OP50 in S-medium leads to the uptake of these nanoparticles through the pharynx and absorption through the gut (Piechulek, Berwanger & Von Mikecz, 2019). We speculate this to be true as well under our conditions.…”

“…We speculate this to be true as well under our conditions. Silica (SiO 2 ) nanoparticles were shown to inhibit the peptide transporter OPT-2/PEP-2, present on the apical layer of the intestinal membrane in C. elegans (Piechulek, Berwanger & Von Mikecz, 2019). Inhibition of the OPT-2/PEP-2 transporter leads to the accumulation of silica nanoparticles in gut granules, indicating they are taken up within the organism.…”

Toxic Effects of Hydroxyl- and Amine-functionalized Silica Nanoparticles (SiO2 and NH2-SiO2 NPs) on Caenorhabditis elegans

“…In general, the wide-range of applications of SiO 2 NPs has increased their rate of manufacture, where in 2014, the global production volume was reported to be 185-1400 kilotons (Keller and Lazareva, 2013;Pulit-Prociak and Banach, 2016). The dispersion of SiO 2 NPs into the environment can be attributed to their end use (Piechulek et al, 2019), and their surface functionalization plays an important role in their environmental fate and transport (Jarvie et al, 2009). Most engineered oxide nanoparticles such as SiO 2 NPs have been observed to be introduced into the environment through industrial wastewater and sewage discharges (Boxall et al, 2007).…”

“…Surface-functionalized SiO 2 NPs as compared to uncoated SiO 2 NPs have been shown to be removed more easily during primary wastewater treatment through the sedimentation process (Jarvie et al, 2009). Other probable routes for SiO 2 NPs released into the air include direct introduction of the particles or through vehicle exhaust, while aerial deposition, leakage, and spills release SiO 2 NPs into surface waters (Bahadar Zeb et al, 2018;Piechulek et al, 2019). Overall, soils and sediments have been observed to be the major environmental sinks of these releases (Piechulek et al, 2019).…”

“…Other probable routes for SiO 2 NPs released into the air include direct introduction of the particles or through vehicle exhaust, while aerial deposition, leakage, and spills release SiO 2 NPs into surface waters (Bahadar Zeb et al, 2018;Piechulek et al, 2019). Overall, soils and sediments have been observed to be the major environmental sinks of these releases (Piechulek et al, 2019). The median SiO 2 NPs levels predicted in central European surface waters had values of 3.5 µg L -1 while natural and urban soils, sewage sludge-treated soil, and landfill waste had values of 160, 390, and 490 µg kg -1 , respectively (Wang et al, 2016;Wang and Nowack, 2018).…”