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Nanoparticle Protein Coronas Differentially Interrogate Proteomes with Superior Performance Compared to Conventional Deep Proteome Workflows

ABSTRACT: The superior performance of a multiple NP workflow was shown compared to high-complexity, state-of-the-art, high-pH fractionation strategies in terms of depth and precision. We also evaluate the link between the physicochemical properties of NPs and their differential protein selectivity.

INSTRUMENT(S): TripleTOF 6600

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Theo Platt

LAB HEAD: Omid Farokhzad

PROVIDER: PXD028634 | Pride | 2022-02-24

REPOSITORIES: Pride

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Engineered nanoparticles enable deep proteomics studies at scale by leveraging tunable nano-bio interactions.

Ferdosi Shadi S Tangeysh Behzad B Brown Tristan R TR Everley Patrick A PA Figa Michael M McLean Matthew M Elgierari Eltaher M EM Zhao Xiaoyan X Garcia Veder J VJ Wang Tianyu T Chang Matthew E K MEK Riedesel Kateryna K Chu Jessica J Mahoney Max M Xia Hongwei H O'Brien Evan S ES Stolarczyk Craig C Harris Damian D Platt Theodore L TL Ma Philip P Goldberg Martin M Langer Robert R Flory Mark R MR Benz Ryan R Tao Wei W Cuevas Juan Cruz JC Batzoglou Serafim S Blume John E JE Siddiqui Asim A Hornburg Daniel D Farokhzad Omid C OC

Proceedings of the National Academy of Sciences of the United States of America 20220311 11

SignificanceDeep profiling of the plasma proteome at scale has been a challenge for traditional approaches. We achieve superior performance across the dimensions of precision, depth, and throughput using a panel of surface-functionalized superparamagnetic nanoparticles in comparison to conventional workflows for deep proteomics interrogation. Our automated workflow leverages competitive nanoparticle-protein binding equilibria that quantitatively compress the large dynamic range of proteomes to a ...[more]

PMID: 35275789

Similar Datasets

Nanoparticle Protein Coronas Differentially Interrogate Proteomes with Superior Performance Compared to Conventional Deep Proteome Workflows

Project description:The superior performance of a multiple NP workflow was shown compared to high-complexity, state-of-the-art, high-pH fractionation strategies in terms of depth and precision. We also evaluate the link between the physicochemical properties of NPs and their differential protein selectivity.

2022-02-24 | PXD022285 | Pride

Proteomics analysis of soybean root exposed to varying sizes of silver nanoparticles under flooding stress

Project description:Because of the tremendous use of NPs in the agricultural sector (Vernikov et al., 2009) and their interactions with the plants, the effect of NPs in plants needs to be explored at the molecular level. To investigate the effects of varying sizes of silver NPs on early-stage soybean under flooding stress, morphological and proteomic analyses were performed. In this study, 5 ppm silver NPs were used because 5 ppm of silver NPs were reported to promote the soybean growth under flooding stress (Mustafa et al., 2015). In the present study, the silver NPs induced changes, in the soybean proteins under flooding stress, was evaluated using gel-free proteomic technique.

2016-08-08 | PXD003711 | Pride

Global genetic impact of surface-modified gold nanoparticles on two model human cell lines

Project description:Gold nanoparticles (Au NPs) are uniquely suited for various biomedical applications due to the combination of their optical properties with their easily functionalized surfaces. The Au NP surface can be tailored to improve biocompatibility while also attaching targeting ligands or drugs. However, information on how these tailored surface chemistries may affect cell gene expression is scarce. Using two model human cells line, human dermal fibroblasts and prostate cancer cells, microarray experiments measured gene expression over 27,000 human genes. Each of the cell lines was exposed to four related types of surface-modified Au NPs at two different concentrations, and the microarray data was analyzed by weighted gene correlation network analysis and gene functional annotation. Au NPs were shown to affect genes associated with a variety of cellular functions, and surface charge and chemistry were linked with the types of parthways changed and the degree of which those changes occured. Nanoparticle induced gene expression in PC3 and HDF cells was measured after 24 hour exposure to nanoparticles of four different surface coating types. RNA from three separate culture samples were used for each nanoparticle-cell combinations, along with three control samples not exposed to nanoparticles at all.

2014-10-01 | E-GEOD-56432 | biostudies-arrayexpress

Nanoparticle Enrichment Mass-Spectrometry Proteomics Identifies Protein Altering Variants for Precise pQTL Mapping

Project description:Proteogenomics studies generate hypotheses on protein function and provide genetic evidence for drug target prioritization. Most previous work has been conducted using affinity-based proteomics approaches. These technological face challenges, such as uncertainty regarding target identity, non-specific binding, and handling of variants that affect epitope affinity binding. Mass spectrometry (MS)-based proteomics can overcome some of these challenges. Here we report a pQTL study using the Proteograph™ Product Suite workflow (Seer, Inc.) where we quantify over 18,000 unique peptides from nearly 3,000 proteins in more than 320 blood samples from a multi-ethnic cohort in a bottom-up, peptide-centric, MS-based proteomics approach. We identify 184 protein-altering variants (PAVs) in 137 genes that are significantly associated with their corresponding variant peptides, confirming target specificity of co-associated affinity binders, identifying putatively causal cis-encoded proteins and providing experimental evidence for their presence in blood, including proteins that may be inaccessible to affinity-based proteomics.

2023-12-19 | PXD042852 | Pride

Differential Gene Expression in Daphnia magna Suggests Distinct Modes of Action and Bioavailability for ZnO nanoparticles and Zn ions

Project description:Zinc Oxide nanoparticles (ZnO NPs) are being rapidly developed for use in consumer products, wastewater treatment and chemotherapy providing several possible routes for ZnO NP exposure to humans and aquatic organisms. Recent studies have shown that ZnO NPs undergo rapid dissolution to Zn+2, but the relative contribution of Zn+2 to ZnO NP bioavailability and toxicity is not clear. Gene expression profiling of D. magna exposed to ZnO NPs or ZnSO4 at equitoxic concentrations demonstrated that the particles cause toxicity through a distinct mechanism compared with Zn+2. D. magna were also exposed to a SiO NPs as a particle control at equimolar concentrations. The SiO NPs resulted in few differentially expressed genes and there was very little overlap between the genes affected by the ZnO NPs and the SiO NPs, suggesting that ZnO NPs cause a distinct pattern of differentially expressed genes. In the ZnO NP exposures, effects were observed to genes involved in cytoskeletal transport, cellular respiration and reproduction. Three biomarker genes including a multi-cystatin, ferritin and a C1q containing gene were confirmed as differentially expressed in a specific pattern by ZnO NP and provide a suite of biomarkers for identifying environmental exposure to ZnO NP and differentiating between NP and ionic exposure. We exposed Daphnia magna to the 1/10 LC50 and LC25 of ZnO nanoparticles and Zn++ as ZnSO4 for 24-h. For each exposure condition, we performed 3 exposures and 2 technical replicates (as dye swap) for each exposure (6 microarrays total). All exposures were compared to a unexposed laboratory control

2010-12-31 | E-GEOD-22051 | biostudies-arrayexpress

Molecular mechanisms underlying zinc oxide nanoparticle induced insulin resistance in mice

Project description:Zinc oxide nanoparticles (ZnO NPs) represent an important class of commercially applied materials. Recently, adverse effects of ZnO NPs were found in humans and animals following ingestion, although the effects on endocrine system disease remain unclear. In this study, ZnO NPs were orally administered to mice, and at doses of 25 mg/kg bw (body weight) ZnO NPs and above, plasma glucose increased significantly. The genome-wide effects of ZnO NPs were then investigated using RNA-sequencing technology. In the cluster analysis, the most significantly enriched Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways concerned membranes and their close association with endoplasmic reticulum (ER) stress and reactive oxygen species (ROS) generation. Biochemical and gene and protein expression analyses revealed that ZnO NPs activated a xenobiotic biodegradation response and increased the expression of cytochrome P450 (CYP) enzymes in mice livers, leading to ER stress. The ER stress increased ROS generation. The high levels of ROS activated the MAPK and NF-B pathways and induced an inflammation response, resulting in the phosphorylation of insulin receptor substrate 1. Thus, the insulin resistance that developed was the primary mechanism for the increase in the plasma glucose of mice treated orally with ZnO NPs.

2022-08-20 | GSE136174 | GEO

Gene expression profile of human endothelial cells with or without nanoparticles

Project description:To understand the the effect of poly(lactic-co-glycolic acid) nanoparticles (NPs) encapsulating a fluorine contrast agent on human umbilical vein endothelial cells (HUVECs), we have employed whole genome microarray expression profiling. The NPs used in this study were prepared in our lab. HUVECs were ordered from Lonza (Cat# C2517A). HUVECs were incubated with NPs for 4 hours. After 4 h, the cells were washed couple of times to remove the NPs and gene expression profiles were detected after 20 h (total time: 24 h) and 7 d in the absence of NPs. HUVECs after 24 h without nanoparticles were used as controls. The gene expression in HUVECs was measured at 24 h and 7 d after incubation with nanoparticles. Three independent experiments were performed at each time.

2014-06-01 | E-GEOD-51661 | biostudies-arrayexpress

RNAseq of human epithelial lung carcinoma cell line A549 exposed to ceria, silver or zinc ions, micron-sized particles or nanoparticles

Project description:The toxicity of silver and zinc oxide nanoparticles is hypothesised to be mediated by dissolved metal ions and cerium dioxide nanoparticles (CeO2 NPs) are hypothesised to induce toxicity specifically by oxidative stress dependant on their surface redox state. To test these hypotheses, RNAseq was applied to characterise the molecular responses of cells to metal nanoparticle and metal ion exposures. The human epithelial lung carcinoma cell line A549 was exposed to different CeO2 NPs with different surface charges, micron-sized and nano-sized silver particles and silver ions, micron-sized and nano-sized zinc oxide particles and zinc ions, or control conditions, for 1 hour, 6 hours and 24 hours. Concentrations were the lower of either EC20 or 128 micrograms/mL. Transcriptional responses were characterised by RNAseq transcriptomics using an Illumina HiSeq2500 .

2018-02-01 | E-MTAB-5734 | biostudies-arrayexpress

Identified small open reading frame encoded peptides in plasma with nanoparticle protein coronas

Project description:We identified small open reading frames encoded peptided in human serum with nanoparticle protein coronas method using mass spectrometry. Four nanoparticle material treatments (TiO2, Fe3O4@SiO2, Fe3O4@SiO2@TiO2, NPs-mix), ACN and untreated control were performed with triplicates. The comparision of 96 well plate and centrifuge tube was carried out with 6 replicates and 4 replicates respectively.

2023-05-24 | PXD042459 | iProX

Modulation of Pulmonary Toxicity in Metabolic Syndrome due to Variations in Nanoparticle-Biocorona Composition

Project description:Following introduction into a biological environment, nanoparticles (NPs) interact with biomolecules forming a biocorona (BC) on their surface altering cell interactions and toxicity. Metabolic syndrome (MetS) is a prevalent condition and enhances susceptibility to inhaled exposures. We hypothesize distinct NP-biomolecule interactions occur in the lungs due to MetS resulting in the formation of unique NP-BCs contributing to enhanced toxicity. Bronchoalveolar lavage fluid (BALF) was collected from healthy and MetS mouse models and used to evaluate variations in the BC formation on 20 nm iron oxide NPs. NPs without or with BCs were characterized for hydrodynamic size and zeta potential. Protein and lipid components of the BCs were evaluated via proteomic and lipidomic assessments. Unique biomolecules were determined to associate with iron oxide NPs while shared biomolecules demonstrated differential abundance based on disease state. A mouse macrophage cell line was utilized to examine alterations in cell interactions and toxicity due to BCs. Exposures for 1h or 24h with NPs did not demonstrate overt cytotoxicity. Darkfield microscopy and X-ray fluorescence (XRF) analysis determined enhanced iron oxide NP internalization due to the MetS BC compared to the healthy BC. Macrophages exposed to NPs with a MetS-BC for 1h or 24h demonstrated enhanced gene expression of inflammatory markers CCL2, IL-6, and TNF-alpha compared to ion oxide NPs with a healthy BC. Inflammatory pathways were examined by western blots to determine activation of specific proteins within the MAP kinase, Jak-Stat, and NF- kB signaling pathways. Activation of STAT3, NF-kB, and ERK pathways were determined to be upregulated due to the MetS-BC. Specifically, the Jak-Stat pathway was determined to be the most upregulated inflammatory pathway following exposure to NPs with a MetS BC.

2022-04-27 | MSV000089322 | MassIVE

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