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Sökning: WFRF:(Cedervall Tommy)

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1.
  • Ali, Neserin, et al. (författare)
  • Analysis of nanoparticle-protein coronas formed in vitro between nanosized welding particles and nasal lavage proteins.
  • 2016
  • Ingår i: Nanotoxicology. - : Taylor & Francis. - 1743-5390 .- 1743-5404. ; 10:2, s. 226-234
  • Tidskriftsartikel (refereegranskat)abstract
    • Welding fumes include agglomerated particles built up of primary nanoparticles. Particles inhaled through the nose will to some extent be deposited in the protein-rich nasal mucosa, and a protein corona will be formed around the particles. The aim was to identify the protein corona formed between nasal lavage proteins and four types of particles with different parameters. Two of the particles were formed and collected during welding and two were manufactured iron oxides. When nasal lavage proteins were added to the particles, differences were observed in the sizes of the aggregates that were formed. Measurements showed that the amount of protein bound to particles correlated with the relative size increase of the aggregates, suggesting that the surface area was associated with the binding capacity. However, differences in aggregate sizes were detected when nasal proteins were added to UFWF and Fe2O3 particles (having similar agglomerated size) suggesting that yet parameters other than size determine the binding. Relative quantitative mass spectrometric and gel-based analyses showed differences in the protein content of the coronas. High-affinity proteins were further assessed for network interactions. Additional experiments showed that the inhibitory function of secretory leukocyte peptidase inhibitor, a highly abundant nasal protein, was influenced by particle binding suggesting that an understanding of protein function following particle binding is necessary to properly evaluate pathophysiological events. Our results underscore the importance of including particles collected from real working environments when studying the toxic effects of particles because these effects might be mediated by the protein corona.
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2.
  • Arosio, Paolo, et al. (författare)
  • Analysis of the length distribution of amyloid fibrils by centrifugal sedimentation
  • 2016
  • Ingår i: Analytical Biochemistry. - : Elsevier BV. - 0003-2697. ; 504, s. 7-13
  • Tidskriftsartikel (refereegranskat)abstract
    • The aggregation of normally soluble peptides and proteins into amyloid fibrils is a process associated with a wide range of pathological conditions, including Alzheimer's and Parkinson's diseases. It has become apparent that aggregates of different sizes possess markedly different biological effects, with aggregates of lower relative molecular weight being associated with stronger neurotoxicity. Yet, although many approaches exist to measure the total mass concentration of aggregates, the ability to probe the length distribution of growing aggregates in solution has remained more elusive. In this work, we applied a differential centrifugation technique to measure the sedimentation coefficients of amyloid fibrils produced during the aggregation process of the amyloid β (M1-42) peptide (Aβ42). The centrifugal method has the advantage of providing structural information on the fibril distribution directly in solution and affording a short analysis time with respect to alternative imaging and analytical centrifugation approaches. We show that under quiescent conditions interactions between Aβ42 fibrils lead to lateral association and to the formation of entangled clusters. By contrast, aggregation under shaking generates a population of filaments characterized by shorter lengths. The results, which have been validated by cryogenic transmission electron microscopy (cryo-TEM) analysis, highlight the important role that fibril-fibril assembly can play in the deposition of aggregation-prone peptides.
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3.
  • Behnen, Petra, et al. (författare)
  • Calcium-Dependent Interaction of Calmodulin with Human 80S Ribosomes and Polyribosomes.
  • 2012
  • Ingår i: Biochemistry. - : American Chemical Society (ACS). - 0006-2960 .- 1520-4995. ; 51:34, s. 6718-6727
  • Tidskriftsartikel (refereegranskat)abstract
    • Ribosomes are the protein factories of every living cell. The process of protein translation is highly complex and tightly regulated by a large number of diverse RNAs and proteins. Earlier studies indicate that Ca(2+) plays a role in protein translation. Calmodulin (CaM), a ubiquitous Ca(2+)-binding protein, regulates a large number of proteins participating in many signaling pathways. Several 40S and 60S ribosomal proteins have been identified to interact with CaM, and here, we report that CaM binds with high affinity to 80S ribosomes and polyribosomes in a Ca(2+)-dependent manner. No binding is observed in buffer with 6 mM Mg(2+) and 1 mM EGTA that chelates Ca(2+), suggesting high specificity of the CaM-ribosome interaction dependent on the Ca(2+) induced conformational change of CaM. The interactions between CaM and ribosomes are inhibited by synthetic peptides comprising putative CaM-binding sites in ribosomal proteins S2 and L14. Using a cell-free in vitro translation system, we further found that these synthetic peptides are potent inhibitors of protein synthesis. Our results identify an involvement of CaM in the translational activity of ribosomes.
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4.
  • Cedervall, Tommy, et al. (författare)
  • Calbindin D-28k EF-hand ligand binding and oligomerization: Four high-affinity sites-three modes of action
  • 2005
  • Ingår i: Biochemistry. - : American Chemical Society (ACS). - 0006-2960 .- 1520-4995. ; 44:41, s. 13522-13532
  • Tidskriftsartikel (refereegranskat)abstract
    • Calbindin D-28k, a highly conserved protein with Ca2+-sensing and Ca2+-buffering capabilities, is abundant in brain and sensory neurons. This protein contains six EF-hand subdomains, four of which bind Call with high affinity. Calbindin D28k can be reconstituted from six synthetic peptides corresponding to the six EF-hands, indicating a single-domain structure with multiple interactions between the EF-hand subdomains. In this study, we have undertaken a detailed characterization of the Ca2+-binding and oligomerization properties of each individual EF-hand peptide using CD spectroscopy and analytical ultracentrifugation. Under the conditions tested, EF2 is monomeric and does not bind Ca2+, whereas EF6, which binds Call weakly, aggregates severely. We have therefore focused this study on the high-affinity binding sites, EF-hands 1, 3, 4, and 5. Our sedimentation equilibrium data show that, in the presence of Call, EF-hands 1, 3, 4, and 5 all form dimers in solution in which the distribution between the monomer, dimer, and higher order oligomers differs. The processes of Call binding and oligomerization are linked to different degrees, and three main mechanisms emerge. For EF-hands 1 and 5, the dimer binds Ca2+ more strongly than the monomer and Call binding drives dimerization. For EF-hand 4, dimer formation requires only one of the monomers to be Ca2+-bound. In this case, the Call affinity is independent of dimerization. For EF-hand 3, dimerization occurs both in the absence and presence of Call, while oligomerization increases in the presence of Ca2+.
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5.
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6.
  • Cedervall, Tommy, et al. (författare)
  • Food chain transport of nanoparticles affects behaviour and fat metabolism in fish.
  • 2012
  • Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 7:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Nano-sized (10(-9)-10(-7) m) particles offer many technical and biomedical advances over the bulk material. The use of nanoparticles in cosmetics, detergents, food and other commercial products is rapidly increasing despite little knowledge of their effect on organism metabolism. We show here that commercially manufactured polystyrene nanoparticles, transported through an aquatic food chain from algae, through zooplankton to fish, affect lipid metabolism and behaviour of the top consumer. At least three independent metabolic parameters differed between control and test fish: the weight loss, the triglycerides∶cholesterol ratio in blood serum, and the distribution of cholesterol between muscle and liver. Moreover, we demonstrate that nanoparticles bind to apolipoprotein A-I in fish serum in-vitro, thereby restraining them from properly utilising their fat reserves if absorbed through ingestion. In addition to the metabolic effects, we show that consumption of nanoparticle-containing zooplankton affects the feeding behaviour of the fish. The time it took the fish to consume 95% of the food presented to them was more than doubled for nanoparticle-exposed compared to control fish. Since many nano-sized products will, through the sewage system, end up in freshwater and marine habitats, our study provides a potential bioassay for testing new nano-sized material before manufacturing. In conclusion, our study shows that from knowledge of the molecular composition of the protein corona around nanoparticles it is possible to make a testable molecular hypothesis and bioassay of the potential biological risks of a defined nanoparticle at the organism and ecosystem level.
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7.
  • Cedervall, Tommy, et al. (författare)
  • Redox sensitive cysteine residues in calbindin D(28)k are structurally and functionally important
  • 2005
  • Ingår i: Biochemistry. - : American Chemical Society (ACS). - 0006-2960 .- 1520-4995. ; 44:2, s. 684-693
  • Tidskriftsartikel (refereegranskat)abstract
    • Human calbindin D-28k is a Ca2+ binding protein that has been implicated in the protection of cells against apoptosis. In this study, the structural and functional significance of the five cysteine residues present in this protein have been investigated through a series of cystein e-to-serine mutations. The mutants were studied under relevant physiological redox potentials in which conformational changes were monitored using ANS binding. Urea-induced denaturations, as monitored by intrinsic tryptophan fluorescence, were also carried out to compare their relative stability. It was shown that the two N-terminal cysteine residues undergo a redox-driven structural change consistent with disulfide bond formation. The other cysteine residues are not by themselves sufficient at inducing structural change, but they accentuate the disulfide-dependent conformational change in a redox-dependent manner. Mass spectrometry data show that the three C-terminal cysteine residues can be modified by glutathione. Furthermore, under oxidizing conditions, the data display additional species consistent with the conversion of cysteine thiols to sulfenic acids and disulfides to disulfide-S-monoxides. The biological function of calbindin D-28k appears to be tied to the redox state of the cysteine residues. The two N-terminal cysteine residues are required for activation of myo-inositol monophosphatase, and enzyme activation is enhanced under conditions in which these residues are oxidized. Last, oxidized calbindin D-28k binds Ca2+ with lower affinity than does the reduced protein.
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8.
  • Cedervall, Tommy (författare)
  • Temperature-dependent structure and function of group A streptococcal M proteins
  • 1999
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Temperature-dependent structure and function of group A streptococcal M proteins.This thesis describes the temperature-dependent structure of the members in the group A streptococcal M protein family. M proteins are cell-surface proteins that are important for the bacterial virulence and bind to a diverse set of human plasma proteins. The proteins are dimeric coiled-coil molecules, but temperature unstable, i.e. at 37°C the isolated proteins are monomeric molecules and to a great extent unfolded. It was shown that the Ig-binding by group A streptococcal strains was weaker at 37°C than 20°C. The Ig-binding by isolated M proteins and M-like proteins was, likewise, weaker at 37°C than 20°C. In contrast, the fibrinogen-binding by bacteria was equally strong at 20°C and 37°C, while the fibrinogen-binding by isolated protein was temperature-dependent. The M protein can be divided into class A and C proteins depending on whether centrally located repeats are A- or C-repeats. The coiled-coil structure of a fibrinogen-binding class A protein, Mrp4, was found to be temperature stable with strong fibrinogen-binding also at 37°C. The class A proteins have a higher percentage of hydrophobic amino acids in residues constituting the hydrophobic core in coiled-coil proteins than class C proteins. This disparity was suggested to explain the different temperature stabilities in class A and C proteins. The temperature stability also varies among class C proteins and higher temperature stability is accompanied by higher percentage hydrophobic amino acids in the hydrophobic core. The unfolding of M proteins indicated one to three structural regions. Furthermore, near-UV circular dichroism studies indicated a lower temperature stability of the N-terminal half of protein H, a class C proteins, compared to the overall helical structure. In opposite, the binding of IgG by protein H stabilised the N-terminal half to a higher extent than the overall helical structure.
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9.
  • Cedervall, Tommy, et al. (författare)
  • Understanding the nanoparticle-protein corona using methods to quantify exchange rates and affinities of proteins for nanoparticles
  • 2007
  • Ingår i: Proceedings of the National Academy of Sciences. - : Proceedings of the National Academy of Sciences. - 1091-6490 .- 0027-8424. ; 104:7, s. 2050-2055
  • Tidskriftsartikel (refereegranskat)abstract
    • Due to their small size, nanoparticles have distinct properties compared with the bulk form of the same materials. These properties are rapidly revolutionizing many areas of medicine and technology. Despite the remarkable speed of development of nanoscience, relatively little is known about the interaction of nanoscale objects with living systems. In a biological fluid, proteins associate with nanoparticles, and the amount and presentation of the proteins on the surface of the particles leads to an in vivo response. Proteins compete for the nanoparticle "surface," leading to a protein "corona" that largely defines the biological identity of the particle. Thus, knowledge of rates, affinities, and stoichiometries of protein association with, and dissociation from, nanoparticles is important for understanding the nature of the particle surface seen by the functional machinery of cells. Here we develop approaches to study these parameters and apply them to plasma and simple model systems, albumin and fibrinogen. A series of copolymer nanoparticles are used with variation of size and composition (hydrophobicity). We show that isothermal titration calorimetry is suitable for studying the affinity and stoichiometry of protein binding to nanoparticles. We determine the rates of protein association and dissociation using surface plasmon resonance technology with nanoparticles that are thiol-linked to gold, and through size exclusion chromatography of protein-nanoparticle mixtures. This method is less perturbing than centrifugation, and is developed into a systematic methodology to isolate nanoparticle-associated proteins. The kinetic and equilibrium binding properties depend on protein identity as well as particle surface characteristics and size.
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10.
  • Cedervall, Tommy, et al. (författare)
  • Workshop on Environmental Nanosafety: Biological Interactions of Plastic Nanoparticles
  • 2019
  • Ingår i: Journal of Chemical Education. - : American Chemical Society (ACS). - 0021-9584 .- 1938-1328. ; 96:9, s. 1967-1970
  • Tidskriftsartikel (refereegranskat)abstract
    • The one-hour workshop, containing both a demonstration and hands-on experiments on the topic of nanosafety, is based on current science on a topic of general interest. The workshop aims to provide a deeper knowledge and understanding of nanoparticles. The participants get an introduction to what nanoparticles are, why nanosized materials are interesting, how nanomaterials interact with biological molecules, and potential risks associated with nanoparticles. Furthermore, by participating in the workshop the audience gains insights into how research about nanoparticles is conducted. The participants carry out experiments to demonstrate that daily-used plastic products can be disintegrated into particles in the nanometer size range, which may have important implications for the environment.
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11.
  • Cukalevski, Risto, et al. (författare)
  • IgG and fibrinogen driven nanoparticle aggregation
  • 2015
  • Ingår i: Nano Reseach. - : Springer Science and Business Media LLC. - 1998-0124 .- 1998-0000. ; 8:8, s. 2733-2743
  • Tidskriftsartikel (refereegranskat)abstract
    • A thorough understanding of how proteins induce nanoparticle (NP) aggregation is crucial when designing in vitro and in vivo assays and interpreting experimental results. This knowledge is also crucial when developing nano-applications and formulation for drug delivery systems. In this study, we found that extraction of immunoglobulin G (IgG) from cow serum results in lower polystyrene NPs aggregation. Moreover, addition of isolated IgG or fibrinogen to fetal cow serum enhanced this aggregation, thus demonstrating that these factors are major drivers of NP aggregation in serum. Counter-intuitively, NP aggregation was inversely dependent on protein concentration; i.e., low protein concentrations induced large aggregates, whereas high protein concentrations induced small aggregates. Protein-induced NP aggregation and aggregate size were monitored by absorbance at 400 nm and dynamic light scattering, respectively. Here, we propose a mechanism behind the protein concentration dependent aggregation; this mechanism involves the effects of multiple protein interactions on the NP surface, surface area limitations, aggregation kinetics, and the influence of other serum proteins.
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12.
  • Cukalevski, Risto, et al. (författare)
  • Structural Changes in Apolipoproteins Bound to Nanoparticles
  • 2011
  • Ingår i: Langmuir. - : American Chemical Society (ACS). - 0743-7463 .- 1520-5827. ; 27:23, s. 14360-14369
  • Tidskriftsartikel (refereegranskat)abstract
    • Nanoparticles are widely used in the pharmaceutical and food industries, but the consequences of exposure to the human body have not been thoroughly investigated. Apolipoprotein A-I (apoAI), the major protein in high-density lipoprotein (HDL), and other lipoproteins are found in the corona around many nanopartides, but data on protein structural and functional effects are lacking. Here we investigate the structural consequences of the adsorption of apoAI, apolipoprotein B100 (apoB100), and HDL on polystyrene nanoparticles with different surface charges. The results of circular dichroism, fluorescence spectroscopy, and limited proteolysis experiments indicate effects on both secondary and tertiary structures. Plain and negatively charged nanoparticles induce helical structure in apoAI (negative net charge) whereas positively charged nanoparticles reduce the amount of helical structure. Plain and negatively charged partides induce a small blue shift in the tryptophan fluorescence spectrum, which is not noticed with the positively charged particles. Similar results are observed with reconstituted HDL. In apoB100, both secondary and tertiary structures are perturbed by all particles. To investigate the generality of the role of surface charge, parallel experiments were performed using human Serum albumin (HSA, negative net charge) and lysozyme (positive net charge). Again, the secondary structure is most affected by nanoparticles carrying an opposite surface charge relative to the protein. Nanoparticles carrying the same net charge as the protein induce only minor structural changes in lysozyme whereas a moderate change is observed for HSA. Thus, surface charge is a critical parameter for predicting structural changes in adsorbed proteins, yet the effect is specific for each protein.
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13.
  • Dell'Orco, Daniele, et al. (författare)
  • Delivery success rate of engineered nanoparticles in the presence of the protein corona: a systems-level screening
  • 2012
  • Ingår i: Nanomedicine: Nanotechnology, Biology and Medicine. - : Elsevier BV. - 1549-9642 .- 1549-9634. ; 8:8, s. 1271-1281
  • Tidskriftsartikel (refereegranskat)abstract
    • Nanoparticles (NPs) for medical applications are often introduced into the body via intravenous injections, leading to the formation of a protein corona on their surface due to the interaction with blood plasma proteins. Depending on its composition and time evolution, the corona will modify the biological behavior of the particle. For successful delivery and targeting, it is therefore important to assess on a quantitative basis how and to what extent the presence of the corona perturbs the specific interaction of a designed NP with its cellular target. We present a theoretical systems-level analysis, in which peptides have been covalently coupled to the surface of nanoparticles, describing the delivery success rate in varying conditions, with regard to protein composition of the surrounding fluid. Dynamic modeling and parameter sensitivity analysis proved to be useful and computationally affordable tools to aid in the design of NPs with increased success rate probability in a biological context. FROM THE CLINICAL EDITOR: The formation of a protein corona consisting of blood plasma proteins on the surface of intravenously delivered nanoparticles may modify the biological behavior of the particles. This team of investigators present a theoretical systems-level analysis of this important and often neglected phenomenon.
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14.
  • Dell'Orco, Daniele, et al. (författare)
  • Mathematical modeling of the protein corona: implications for nanoparticulate delivery systems
  • 2014
  • Ingår i: Nanomedicine. - 1743-5889. ; 9:6, s. 851-858
  • Tidskriftsartikel (refereegranskat)abstract
    • This article discusses the role of the protein corona in delivery systems with tagged nanoparticles and how knowledge of the protein corona can help in optimizing delivery. The basic question is whether and how the binding of proteins and other biomolecules at the nanoparticle surface interfere with the interaction between a tag and its receptor. This is an interesting problem in many respects, but most intriguing are the observed differences in delivery efficiency in vivo compared with protein-free in vitro conditions. In order to understand possible situations that the nanoparticle will face in a protein-rich biological environment, we will first describe the formation of a protein corona and thereafter discuss potential perturbations of the delivery systems when moving from in vitro testing to in vivo applications. We emphasize the role of mathematical modeling in optimizing the design of functionalized nanoparticles to achieve high success of delivery.
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15.
  • Dell'Orco, Daniele, et al. (författare)
  • Mathematical modeling of the protein corona : Implications for nanoparticulate delivery systems
  • 2016. - 2
  • Ingår i: Handbook of Immunological Properties of Engineered Nanomaterials: : Haematocompatibility of Engineered Nanomaterials - Haematocompatibility of Engineered Nanomaterials. - : WORLD SCIENTIFIC. - 9789814699167 - 9789814699174 ; 2, s. 53-65
  • Bokkapitel (refereegranskat)abstract
    • This article discusses the role of the protein corona in delivery systems with tagged nanoparticles and how knowledge of the protein corona can help in optimizing delivery. The basic question is whether and how the binding of proteins and other biomolecules at the nanoparticle surface interfere with the interaction between a tag and its receptor. This is an interesting problem in many respects, but most intriguing are the observed differences in delivery effi ciency in vivo compared with protein-free in vitro conditions. In order to understand possible situations that the nanoparticle will face in a protein-rich biological environment, we will fi rst describe the formation of a protein corona and thereafter discuss potential perturbations of the delivery systems when moving from in vitro testing to in vivo applications. We emphasize the role of mathematical modeling in optimizing the design of functionalized nanoparticles to achieve high success of delivery.
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16.
  • Dell'Orco, Daniele, et al. (författare)
  • Modeling the Time Evolution of the Nanoparticle-Protein Corona in a Body Fluid
  • 2010
  • Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 5
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Nanoparticles in contact with biological fluids interact with proteins and other biomolecules, thus forming a dynamic corona whose composition varies over time due to continuous protein association and dissociation events. Eventually equilibrium is reached, at which point the continued exchange will not affect the composition of the corona. Results: We developed a simple and effective dynamic model of the nanoparticle protein corona in a body fluid, namely human plasma. The model predicts the time evolution and equilibrium composition of the corona based on affinities, stoichiometries and rate constants. An application to the interaction of human serum albumin, high density lipoprotein (HDL) and fibrinogen with 70 nm N-iso-propylacrylamide/N-tert-butylacrylamide copolymer nanoparticles is presented, including novel experimental data for HDL. Conclusions: The simple model presented here can easily be modified to mimic the interaction of the nanoparticle protein corona with a novel biological fluid or compartment once new data will be available, thus opening novel applications in nanotoxicity and nanomedicine.
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17.
  • Ekvall, Mikael T., et al. (författare)
  • Adsorption of bio-organic eco-corona molecules reduces the toxic response to metallic nanoparticles in Daphnia magna
  • 2021
  • Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 11:1
  • Tidskriftsartikel (refereegranskat)abstract
    • As the use of engineered nanomaterials increases, so does the risk of them spreading to natural ecosystems. Hitherto, knowledge regarding the toxic properties of nanoparticles (NP's) and their potential interactions with natural bio-organic molecules adsorbed to them, and thereby forming surface coronas, is limited. However, we show here that the toxic effect of NPs of tungsten carbide cobalt (WC-Co) and cobalt (Co) on the crustacean Daphnia magna is postponed in the presence of natural biological degradation products (eco-corona biomolecules). For Daphnia exposed to WC-Co NPs the survival time increased with 20-25% and for Co NPs with 30-47% after mixing the particles with a solution of eco-corona biomolecules before exposure. This suggests that an eco-corona, composed of biomolecules always present in natural ecosystems, reduces the toxic potency of both studied NPs. Further, the eco-coronas did not affect the particle uptake, suggesting that the reduction in toxicity was related to the particle-organism interaction after eco-corona formation. In a broader context, this implies that although the increasing use and production of NPs may constitute a novel, global environmental threat, the acute toxicity and long-term effects of some NPs will, at least under certain conditions, be reduced as they enter natural ecosystems.
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18.
  • Ekvall, Mikael T., et al. (författare)
  • Environmental impact of nanoplastics from fragmentized consumer plastics : Final project report
  • 2022
  • Rapport (övrigt vetenskapligt/konstnärligt)abstract
    • Misplaced plastics is an ongoing environmental problem. The breakdown of plastics into smaller pieces, microplastics, likely cause additional environmental burdens as they affect animals and plants at the beginning of the food chain. This may be even more true for the smallest of microplastics: the nano plastics as they will behave differently in nature and interact in new ways with organisms and potentially be taken up by the organisms and affect internal organs. The small size of nano plastics and their chemical resemblance with the surrounding environment makes them difficult to find, isolate and study. Most of what is known about nano plastics behavior in nature and their effect on nature derives from studies using commercially available polystyrene nanoparticles. These are probably different in many ways, such as structure, surface chemistry, and size distribution, compared to nano plastics broken down in nature from plastic debris. Despite this, we have used polystyrene nanoparticles to study knowledge gaps. The toxicity to zooplankton Daphnia magna (D. magna) of small positively charged amine-modified polystyrene nanoparticles is not affected by protein-induced aggregation. All tested polystyrene nanoparticles were toxic to D. magna regardless of their toxicity in acute tests. Proteins bound to polystyrene nanoparticles after filtration by D. magna were different on acutely and non-acutely toxic particles which may imply different mechanisms behind the toxicity. In order to study the effect of nano plastics that resemble what can be expected in nature we have mechanically broken down 8 different plastics and rubbers from 14 different consumer products and isolated the nano plastics. Careful characterization shows that the nano plastics are irregular in shape, have a slightly negative surface charge, and often have a strongly oxidized surface compared to the starting material. The nano sized fractions are not toxic to D. magna in the used concentrations. In contrary, for at least two plastics High Density Polyethylene (HDPE) and Polylactic acid (PLA) thoracoplasties increase the lifetime of the D. magna probably because the nano plastics can be utilized by bacteria which in turn serve as additional food for the zooplankton. However, leached additives and/or smaller polymers from HDPE are toxic to D. magna. We have also seen that UV irradiation further degrade polystyrene nanoparticles. The bacterial growth and the UV breakdown may imply that the nano plastics breakdown faster than believed in nature and that they with time may disappear.
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19.
  • Ekvall, Mikael T., et al. (författare)
  • Long-term effects of tungsten carbide (WC) nanoparticles in pelagic and benthic aquatic ecosystems
  • 2018
  • Ingår i: Nanotoxicology. - : Taylor & Francis. - 1743-5390 .- 1743-5404. ; 12:1, s. 79-89
  • Tidskriftsartikel (refereegranskat)abstract
    • As the production and usage of nanomaterials are increasing so are the concerns related to the release of the material into nature. Tungsten carbide (WC) is widely used for its hard metal properties, although its use, in for instance tyre studs, may result in nano-sized particles ending up in nature. Here, we evaluate the potential long-term exposure effects of WC nanoparticles on a pelagic (Daphnia magna) and a benthic (Asellus aquaticus) organism. No long-term effects were observed in the benthic system with respect to population dynamics or ecosystem services. However, long-term exposure of D. magna resulted in increased time to first reproduction and, if the particles were resuspended, strong effects on survival and reproductive output. Hence, the considerable differences in acute vs. long-term exposure studies revealed here emphasize the need for more long-term studies if we are to understand the effects of nanoparticles in natural systems.
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20.
  • Ekvall, Mikael T., et al. (författare)
  • Nanoplastics formed during the mechanical breakdown of daily-use polystyrene products
  • 2019
  • Ingår i: Nanoscale Advances. - : Royal Society of Chemistry (RSC). - 2516-0230. ; 1:3, s. 1055-1061
  • Tidskriftsartikel (refereegranskat)abstract
    • Large amounts of plastics are released into the environment every day. These released plastics have a clearly documented negative effect on wildlife. Much research attention has been given to large plastic pieces and microplastics. However, if the breakdown of plastics is a continous process, eventually nanoplastics will be produced. Nanoplastics will affect wildlife differently from larger plastic pieces. We have studied the products formed by the mechanical breakdown of two commonly used polystyrene products, takeaway coffee cup lids and expanded polystyrene foam. After breakdown using a food processor, we characterized the breakdown products using seven different methods and found nanosized polystyrene particles with different shapes and negative or nearly neutral surface charges. These results clearly demonstrate that daily-use polystyrene products can break down into nanoparticles. Model polystyrene particles with different sizes and surface modifications have previously been shown to have different negative effects on wildlife. This indicates that breakdown nanoparticles might have the potential to cause cocktail effects in nature.
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21.
  • Ekvall, Mikael T., et al. (författare)
  • Nanoplastics released from daily used silicone and latex products during mechanical breakdown
  • 2023
  • Ingår i: PLoS ONE. - 1932-6203. ; 18:9
  • Tidskriftsartikel (refereegranskat)abstract
    • Waste of polymer products, especially plastics, in nature has become a problem that caught the awareness of the general public during the last decade. The macro- and micro polymers in nature will be broken down by naturally occurring events such as mechanical wear and ultra-violet (UV) radiation which will result in the generation of polymeric particles in the nano-size range. We have recently shown that polystyrene and high-density polyethylene macroplastic can be broken down into nano-sized particles by applying mechanical force from an immersion blender. In this article, we show that particles in the nano-size range are released from silicone and latex pacifiers after the same treatment. Additionally, boiling the pacifiers prior to the mechanical breakdown process results in an increased number of particles released from the silicone but not the latex pacifier. Particles from the latex pacifier are acutely toxic to the freshwater filter feeding zooplankter Daphnia magna.
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22.
  • Ekvall, Mikael T, et al. (författare)
  • Size fractionation of high-density polyethylene breakdown nanoplastics reveals different toxic response in Daphnia magna
  • 2022
  • Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 12, s. 3109-3109
  • Tidskriftsartikel (refereegranskat)abstract
    • Plastic litter is a growing environmental problem. Recently, microplastics and nanoplastics, produced during breakdown processes in nature, have been in focus. Although there is a growing knowledge concerning microplastic, little is still known about the effect of nanoplastics. We have showed that mechanical breakdown of high-density polyethylene (HDPE), followed by filtration through 0.8 µm filters, produces material toxic to the freshwater zooplankton Daphnia magna and affected the reproduction in life-time tests. However, further size fractionation and purification reveals that the nanoplastics fraction is non-toxic at these concentrations, whereas the fraction with smaller sizes, below ~ 3 nm, is toxic. The HDPE nanoplastics are highly oxidized and with an average diameter of 110 nm. We conclude that mechanical breakdown of HDPE may cause environmental problems, but that the fraction of leached additives and short chain HDPE are more problematic than HDPE nanoplastics.
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23.
  • Ekvall, Mikael T., et al. (författare)
  • The forgotten tonsils—does the immune active organ absorb nanoplastics?
  • 2022
  • Ingår i: Frontiers in Nanotechnology. - : Frontiers Media SA. - 2673-3013. ; 4
  • Tidskriftsartikel (refereegranskat)abstract
    • Nanoplastics are defined as plastic particles broken down to extremely small sizes (1–100 nm) with unknown effects to the human body and immune system. Air and food exposure scenarios involving blood, lungs and intestine are considered in the literature. The fact that plastics also needs to pass the nose, oral cavity, and throat is so far ignored in the literature. The tonsils are immunologically important tissue in the oral cavity in which ingested and inhaled agents are incorporated through crypts with the capacity to capture agents and start early immunologic reactions. We argue that the tonsil is a very important tissue to study in regard to micro and nanoplastic human exposure and immunologic response. Nano-sized particles are known to be able to travel through the natural barriers and have different effects on biology compared to larger particle and the bulk material. It is therefore, although difficult, important to develop experimental methods to detect and identify nanoplastics in the tonsils. In preliminary experiments we have optimized the breakdown of tonsil tissues and tried to retrieve added polystyrene nanoparticles using density-based separation and concentration. The polystyrene was followed by FTIR spectrometry and could be detected in micro- and nano-size, in the tissue breakdown solution but not after density-based separation. When nanoplastics are incorporated in the human body, it is possible that the small plastic pieces can be detected in the tonsil tissue, in the lymph system and it is of importance for future studies to reveal the immunological effects for humans.
  •  
24.
  • Ferreira, Silvia A., et al. (författare)
  • Biocompatibility of mannan nanogel-safe interaction with plasma proteins
  • 2012
  • Ingår i: Biochimica et Biophysica Acta. General Subjects. - : Elsevier BV. - 0304-4165. ; 1820:7, s. 1043-1051
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Self-assembled mannan nanogels are designed to provide a therapeutic or vaccine delivery platform based on the bioactive properties of mannan to target mannose receptor expressed on the surface of antigen-presenting cells, combined with the performance of nanogels as carriers of biologically active agents. Methods: Proteins in the corona around mannan nanogel formed in human plasma were identified by mass spectrometry after size exclusion chromatography or centrifugation followed by sodium dodecyl sulfate polyacrylamide gel electrophoresis. Structural changes and time dependent binding of human apolipoprotein A-I (apoA-I) and human serum albumin (HSA) to mannan nanogel were studied using intrinsic tryptophan fluorescence and circular dichroism spectroscopy. The mannan nanogel effect on blood coagulation and fibrillation of Alzheimer's disease-associated amyloid beta peptide and hemodialysis-associated amyloidosis beta 2 microglobulin was evaluated using thrombin generation assay or thioflavin T fluorescence assay, respectively. Results: The protein corona around mannan nanogel is formed through a slow process, is quite specific comprising apolipoproteins B-100, A-I and E and HSA, evolves over time, and the equilibrium is reached after hours to days. Structural changes and time dependent binding of apoA-I and HSA to mannan nanogel are minor. The mannan nanogel does not affect blood coagulation and retards the fibril formation. Conclusions: Mannan nanogel has a high biosafety and biocompatibility, which is mandatory for nanomaterials to be used in biomedical applications. General Significance: Our research provides a molecular approach to evaluate the safety aspects of nanomaterials, which is of general concern in society and science. (C) 2012 Elsevier B.V. All rights reserved.
  •  
25.
  • Frankel, Rebecca, et al. (författare)
  • Autocatalytic amplification of Alzheimer-associated Aβ42 peptide aggregation in human cerebrospinal fluid
  • 2019
  • Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 2:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Alzheimer’s disease is linked to amyloid β (Aβ) peptide aggregation in the brain, and a detailed understanding of the molecular mechanism of Aβ aggregation may lead to improved diagnostics and therapeutics. While previous studies have been performed in pure buffer, we approach the mechanism in vivo using cerebrospinal fluid (CSF). We investigated the aggregation mechanism of Aβ42 in human CSF through kinetic experiments at several Aβ42 monomer concentrations (0.8–10 µM). The data were subjected to global kinetic analysis and found consistent with an aggregation mechanism involving secondary nucleation of monomers on the fibril surface. A mechanism only including primary nucleation was ruled out. We find that the aggregation process is composed of the same microscopic steps in CSF as in pure buffer, but the rate constant of secondary nucleation is decreased. Most importantly, the autocatalytic amplification of aggregate number through catalysis on the fibril surface is prevalent also in CSF.
  •  
26.
  • Frankel, Rebecca, et al. (författare)
  • Controlled protein mediated aggregation of polystyrene nanoplastics does not reduce toxicity towards Daphnia magna
  • 2020
  • Ingår i: Environmental Science: Nano. - : Royal Society of Chemistry (RSC). - 2051-8153 .- 2051-8161. ; 7:5, s. 1518-1524
  • Tidskriftsartikel (refereegranskat)abstract
    • Microplastics have recently become a growing environmental issue, whereas the smaller fractions, nanoplastics, have received less attention. Due to their small size, nanoplastics may affect organisms differently and potentially more severely than larger microplastics. In natural environments nanoplastics also interact with organic material and form larger aggregates, which may, potentially, reduce their toxicity as they grow in size. We tested the change in toxicity towards Daphnia magna by controlling the size of the aggregates of positively charged 50 nm polystyrene nanoplastics, which are highly toxic as single particles. We show that although 200 to 500 nm nanoplastics are not toxic, aggregates of 50 nm nanoplastics in the same size range are at least as toxic as the free, 50 nm, nanoplastics. Hence, an increase in size through aggregation, a process likely to occur as nanoparticles enter natural ecosystems, does not reduce toxicity. In a broader context this finding provides a firm basis for societal decision making regarding the potency of nanoparticles as they enter natural ecosystems.
  •  
27.
  • Frost, Rickard, 1979, et al. (författare)
  • Real-time in situ analysis of biocorona formation and evolution on silica nanoparticles in defined and complex biological environments
  • 2017
  • Ingår i: Nanoscale. - : Royal Society of Chemistry (RSC). - 2040-3372 .- 2040-3364. ; 9:10, s. 3620-3628
  • Tidskriftsartikel (refereegranskat)abstract
    • Biomolecules such as proteins immediately adsorb on the surface of nanoparticles upon their exposure to a biological environment. The formed adlayer is commonly referred to as biomolecule corona (biocorona) and defines the biological activity and toxicity of the nanoparticle. Therefore, it is essential to understand in detail the biocorona formation process, and how it is governed by parameters like composition of the biological environment, and nanoparticle size, shape and faceting. Here we present a detailed equilibrium and real time in situ study of biocorona formation at SiO2-nanoparticle surfaces upon exposure to defined (BSA, IgG) and complex (bovine serum, IgG depleted bovine serum) biological samples. We use both nanofabricated surface-associated Au core-SiO2 shell nanoparticles (faceted, d = 92-167 nm) with integrated nanoplasmonic sensing function and dispersed SiO2 nanoparticles (using DLS and SDS-PAGE). The results show that preadsorbed BSA or IgG are exchanged for other proteins when exposed to bovine serum. In addition, the results show that IgG forms a biocorona with different properties at curved (edge) and flat (facet) SiO2-nanoparticle surfaces. Our study paves the way for further real time in situ investigations of the biocorona formation and evolution kinetics, as well as the role of molecular orientation in biocorona formation, on nanoparticles with surface faceting.
  •  
28.
  • Gerlt, Michael, et al. (författare)
  • Reducing the Impact of Bias in Oral Assessments
  • 2023
  • Ingår i: LTH:s 12:e Pedagogiska Inspirationskonferens, 7 december 2023. - 2003-3761. ; 2023
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • Oral assessment is an important method to evaluate the learning outcomes of scientific courses. However,there are certain limitations when oral assessment is applied.One of these limitations, which is not apparent in anonymous written exams, is the existence of biases which could lead to unfair (positive or negative) outcomes of the assessment. This could lead to decreased motivation and sense of belonging among minority student groups, potentially upholding or even increasing inequalities. The major issue with biases is that most of them are unconscious, meaning that it is very tough to mitigate. In this manuscript, we analyze the emergence and effect of expectancy-based bias through personal construct theory in order to find approaches to reduce the influence of bias in oral assessment. As such, we address biases existing before interaction with the student (stereotype), emerging from interaction with the student (halo bias), and how these can contribute to a biased idea of the student in the evaluator’s mind. We finally discuss how this can cause cognitive dissonance and biased assessment when student performance is not in line with the teacher's cognitive model of the student and propose solutions on how to deal with this to minimize bias in oral assessment.
  •  
29.
  • Gunnarsson, Stefán B., et al. (författare)
  • Analysis of complexes formed by small gold nanoparticles in low concentration in cell culture media
  • 2019
  • Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 14:6
  • Tidskriftsartikel (refereegranskat)abstract
    • New nanomaterials are constantly developed with applications in everything from cosmetics to high tech electronics. Assessing their biological impact has been done by analysis of their adsorbed protein corona, in vitro cell assays, and larger scale ecotoxicological studies. This has proved to be a huge challenge due to the wide range of available nanomaterials and their unpredictable behaviour in different environments. Furthermore, the enormous number of experimental variables make comparisons difficult. Concentration is one of these variables and can vary greatly depending on the aim of the study. When analysing the protein corona, concentrations are often higher than in cell assays. Using a combination of complementary techniques, we have characterised 20 nm gold nanoparticles in a concentration level commonly used in cell studies. We compare their behaviour in a commonly used, protein rich medium and one protein poor medium over 24 hours. Under these conditions, the NPs were stable in protein rich environment but underwent gradual aggregation in protein poor medium. We characterise the biomolecular corona in both media. In protein poor medium, we can describe the often overlooked aggregation. The aggregates' morphology is confirmed by cryo-TEM. Finally, in the protein poor medium, by infrared spectroscopy, we have identified the amino acid arginine in the biomolecular corona which drives the aggregation.
  •  
30.
  • Gunnarsson, Stefán B., et al. (författare)
  • Analysis of nanoparticle biomolecule complexes
  • 2018
  • Ingår i: Nanoscale. - : Royal Society of Chemistry (RSC). - 2040-3364 .- 2040-3372. ; 10:9, s. 4246-4257
  • Tidskriftsartikel (refereegranskat)abstract
    • Nanoparticles exposed to biological fluids adsorb biomolecules on their surface forming a biomolecular corona. This corona determines, on a molecular level, the interactions and impact the newly formed complex has on cells and organisms. The corona formation as well as the physiological and toxicological relevance are commonly investigated. However, an acknowledged but rarely addressed problem in many fields of nanobiotechnology is aggregation and broadened size distribution of nanoparticles following their interactions with the molecules of biological fluids. In blood serum, TiO2 nanoparticles form complexes with a size distribution from 30 nm to more than 500 nm. In this study we have separated these complexes, with good resolution, using preparative centrifugation in a sucrose gradient. Two main apparent size populations were obtained, a fast sedimenting population of complexes that formed a pellet in the preparative centrifugation tube, and a slow sedimenting complex population still suspended in the gradient after centrifugation. Concentration and surface area dependent differences are found in the biomolecular corona between the slow and fast sedimenting fractions. There are more immunoglobulins, lipid binding proteins, and lipid-rich complexes at higher serum concentrations. Sedimentation rate and the biomolecular corona are important factors for evaluating any experiment including nanoparticle exposure. Our results show that traditional description of nanoparticles in biological fluids is an oversimplification and that more thorough characterisations are needed.
  •  
31.
  • Gunnarsson, Stefán Bragi, et al. (författare)
  • Dual topography of laminin corona on gallium arsenide nanowires
  • 2020
  • Ingår i: Biointerphases. - : American Vacuum Society. - 1934-8630 .- 1559-4106. ; 15:5
  • Tidskriftsartikel (refereegranskat)abstract
    • Nanowires (NWs) are novel nanomaterials with applications in everything from medical implants to solar cells. With increasing number of applications, it is increasingly likely that organisms are exposed to these materials either intentionally or by accident. It is, therefore, important to study their interactions with biological systems and biomolecules. Upon exposure to biological fluids, nanostructure surfaces are quickly covered by a biomolecule corona. The composition of the corona determines the nanostructure's biological fate. Furthermore, upon adsorption, the protein structure can be affected. In order to study the corona morphology, we used two model proteins, laminin of the extracellular matrix and the immune system enzyme myeloperoxidase. We image the protein corona directly by cryo-TEM and enhance resolution by labeling the corona with activated gold nanoparticles. Three-dimensional imaging of the protein corona further increases the resolution and reveals irregularities in corona topography. By doing so, we identified bimodal distribution of spacing between gold nanoparticles and the NW surface for laminin corona at 58 and 85 nm distance from the NWs' surface. The dual topography of the corona is adding a new complexity of the protein corona surface and its interactions with the surrounding biology.
  •  
32.
  • Hedberg, Jonas, 1979-, et al. (författare)
  • Tungsten carbide nanoparticles in simulated surface water with natural organic matter : dissolution, agglomeration, sedimentation and interaction with Daphnia magna
  • 2017
  • Ingår i: Environmental Science: Nano. - : Royal Society of Chemistry. - 2051-8153 .- 2051-8161. ; 4:4, s. 886-894
  • Tidskriftsartikel (refereegranskat)abstract
    • Even though anthropogenic nano-sized tungsten carbide nanoparticles (WC NPs) have been found in the environment, there are currently no investigations on their environmental fate. This work studies the interaction between natural organic matter (NOM) and WC NPs, as well as the potential uptake by the aquatic model organism Daphnia magna. We here show that the affinity between WC NPs and humic acid or dihydroxybenzoic acid (DHBA), which are model molecules of NOM, is very low with no observed surface adsorption. The lack of a stabilizing effect of these organic molecules, in combination with a relatively high effective density of WC NP agglomerates in humic acid, resulted in the substantial agglomeration and sedimentation of the WC NPs. A higher stability of the smaller sized WC NP agglomerates (<150 nm) means that this fraction is mobile and can be transported to other settings, suggesting that this particle fraction should be considered in further studies. The dissolution of tungsten from WC NPs was continuous and the relatively slow dissolution rate (on the order of 0.03 mg m-2 h-1) implies that particle transport will not be severely limited from a dissolution perspective. Uptake of tungsten (dissolved tungsten and WC particles) by D. magna was observed although this did not induce any acute toxic effects.
  •  
33.
  • Hellstrand, Erik, et al. (författare)
  • Complete high-density lipoproteins in nanoparticle corona.
  • 2009
  • Ingår i: The FEBS Journal. - : Wiley. - 1742-464X .- 1742-4658. ; 276:12, s. 3372-3381
  • Tidskriftsartikel (refereegranskat)abstract
    • In a biological environment, nanoparticles immediately become covered by an evolving corona of biomolecules, which gives a biological identity to the nanoparticle and determines its biological impact and fate. Previous efforts at describing the corona have concerned only its protein content. Here, for the first time, we show, using size exclusion chromatography, NMR, and pull-down experiments, that copolymer nanoparticles bind cholesterol, triglycerides and phospholipids from human plasma, and that the binding reaches saturation. The lipid and protein binding patterns correspond closely with the composition of high-density lipoprotein (HDL). By using fractionated lipoproteins, we show that HDL binds to copolymer nanoparticles with much higher specificity than other lipoproteins, probably mediated by apolipoprotein A-I. Together with the previously identified protein binding patterns in the corona, our results imply that copolymer nanoparticles bind complete HDL complexes, and may be recognized by living systems as HDL complexes, opening up these transport pathways to nanoparticles. Apolipoproteins have been identified as binding to many other nanoparticles, suggesting that lipid and lipoprotein binding is a general feature of nanoparticles under physiological conditions.
  •  
34.
  • Hjort, Martin, et al. (författare)
  • Electron microscopy imaging of proteins on gallium phosphide semiconductor nanowires
  • 2016
  • Ingår i: Nanoscale. - : Royal Society of Chemistry (RSC). - 2040-3372 .- 2040-3364. ; 8:7, s. 3936-3943
  • Tidskriftsartikel (refereegranskat)abstract
    • We have imaged GaP nanowires (NWs) incubated with human laminin, serum albumin (HSA), and blood plasma using both cryo-transmission electron microscopy and synchrotron based X-ray photoemission electron microscopy. This extensive imaging methodology simultaneously reveals structural, chemical and morphological details of individual nanowires and the adsorbed proteins. We found that the proteins bind to NWs, forming coronas with thicknesses close to the proteins' hydrodynamic diameters. We could directly image how laminin is extending from the NWs, maximizing the number of proteins bound to the NWs. NWs incubated with both laminin and HSA show protein coronas with a similar appearance to NWs incubated with laminin alone, indicating that the presence of HSA does not affect the laminin conformation on the NWs. In blood plasma, an intermediate sized corona around the NWs indicates a corona with a mixture of plasma proteins. The ability to directly visualize proteins on nanostructures in situ holds great promise for assessing the conformation and thickness of the protein corona, which is key to understanding and predicting the properties of engineered nanomaterials in a biological environment.
  •  
35.
  • Hua, Jing, et al. (författare)
  • Environmental risks of breakdown nanoplastics from synthetic football fields
  • 2024
  • Ingår i: Environmental Pollution. - 0269-7491. ; 347
  • Tidskriftsartikel (refereegranskat)abstract
    • The widespread use of synthetic turf in sports has raised health concerns due to potential risks from nanoplastic inhalation or ingestion. Our research focused on detecting nanoplastics in drainage water from a synthetic football field and evaluating the toxicity of these materials after mechanical fragmentation. We collected and analysed drainage water samples for polymer content and subjected high-density polyethylene (HDPE) straws and ethylene propylene diene monomer (EPDM) granules used on synthetic football fields, to mechanical breakdown to create nanoplastics. The results indicated the presence of trace amounts of EPDM in the water samples. Furthermore, the toxicological assessment revealed that the broken-down nanoplastics and leachate from the surface of EPDM rubber granules exhibited high toxicity to Daphnia magna, while nanoplastics from the inner material exhibited no significant toxicity. The findings highlight the urgent need for future research to identify these specific toxic agents from the surface of EPDM granules.
  •  
36.
  • Kaur, Jasreen, et al. (författare)
  • Label-free detection of polystyrene nanoparticles in Daphnia magna using Raman confocal mapping
  • 2023
  • Ingår i: Nanoscale Advances. - : Royal Society of Chemistry. - 2516-0230. ; 5:13, s. 3453-
  • Tidskriftsartikel (refereegranskat)abstract
    • Micro- and nanoplastic pollution has emerged as a global environmental problem. Moreover, plastic particles are of increasing concern for human health. However, the detection of so-called nanoplastics in relevant biological compartments remains a challenge. Here we show that Raman confocal spectroscopy-microscopy can be deployed for the non-invasive detection of amine-functionalized and carboxy-functionalized polystyrene (PS) nanoparticles (NPs) in Daphnia magna. The presence of PS NPs in the gastrointestinal (GI) tract of D. magna was confirmed by using transmission electron microscopy. Furthermore, we investigated the ability of NH2-PS NPs and COOH-PS NPs to disrupt the epithelial barrier of the GI tract using the human colon adenocarcinoma cell line HT-29. To this end, the cells were differentiated for 21 days and then exposed to PS NPs followed by cytotoxicity assessment and transepithelial electrical resistance measurements. A minor disruption of barrier integrity was noted for COOH-PS NPs, but not for the NH2-PS NPs, while no overt cytotoxicity was observed for both NPs. This study provides evidence of the feasibility of applying label-free approaches, i.e., confocal Raman mapping, to study PS NPs in a biological system. 
  •  
37.
  • Kelpsiene, Egle, et al. (författare)
  • Long-term exposure to nanoplastics reduces life-time in Daphnia magna
  • 2020
  • Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10
  • Tidskriftsartikel (refereegranskat)abstract
    • Plastics are widely used in todays society leading to an accelerating amount of plastic waste entering natural ecosystems. Over time these waste products degrade to micro- and, eventually, nanoplastic particles. Therefore, the break-down of plastics may become a critical threat to aquatic ecosystems and several short term studies have demonstrated acute toxicity of nanoplastics on aquatic organisms. However, our knowledge about effects of chronic or life-time exposure on freshwater invertebrates remains elusive. Here, we demonstrate results from life-time exposure (103 days) of a common freshwater invertebrate, Daphnia magna, exposed to sub-lethal concentrations of polystyrene nanoparticles. 53 nm positively charged aminated polystyrene particles were lethal at concentration of 0.32 mg/L which is two magnitudes lower than previously used concentrations in short-term (24 h) tests. At this concentration the life-time of individuals was shortened almost three times. Negatively charged carboxylated 26 and 62 nm polystyrene particles, previously demonstrated to be non-toxic at 25 and 50 mg/L concentrations in short-term tests, were toxic to D. magna at all concentrations used in our long-term study. Although total reproductive output was not significantly affected at increasing concentrations of polystyrene nanoparticles, there was a decreasing trend in the number of offspring over their life-time. Hence, in order to understand how the potential future environmental problem of nanoplastic particles may affect biota, long-term or life-time studies resembling environmental concentrations should be performed in order to provide information for predictions of future scenarios in natural aquatic environments.
  •  
38.
  • Kelpsiene, Egle, et al. (författare)
  • Metabolomics-based analysis in Daphnia magna after exposure to low environmental concentrations of polystyrene nanoparticles
  • 2023
  • Ingår i: Environmental Science: Nano. - 2051-8153. ; 10:7, s. 1858-1866
  • Tidskriftsartikel (refereegranskat)abstract
    • Larger plastic pieces break down into micro- and eventually nano-sized plastics. This makes nanoplastics ubiquitous in the environment, giving rise to great concern for its effect on biota. Many studies use polystyrene nanoparticles (PS-NPs) as a model for nanoplastics, showing a negative impact on various organisms, but the molecular effects are yet not fully explored. Here we applied 1H nuclear magnetic resonance (NMR) metabolomics to characterize the metabolic changes in Daphnia magna during long-term (37 days) exposure to low concentrations of positively and negatively charged (aminated and carboxylated) PS-NPs. We show that exposure to PS-NPs at concentrations down to 3.2 μg L−1 affected amino acid metabolism and the bacterial metabolite isopropanol in D. magna. These effects were largely independent of particle concentration and surface charge. The results highlight the importance of (1) performing chronic exposures under low concentrations and (2) further investigation of particles with different surface charges.
  •  
39.
  • Kelpsiene, Egle, et al. (författare)
  • Prolonged survival time of Daphnia magna exposed to polylactic acid breakdown nanoplastics
  • 2023
  • Ingår i: PLoS ONE. - 1932-6203. ; 18:9
  • Tidskriftsartikel (refereegranskat)abstract
    • Polylactic acid nanoparticles (PLA NPs) according to food and drug administration are biodegradable and biocompatible polymers that have received a lot of attention due to their natural degradation mechanism. Although there is already available information concerning the effects of PLA microplastic to aquatic organisms, the knowledge about PLA NPs is still vague. In the present study, we analyzed the chemical composition of engineered PLA NPs, daily used PLA items and their breakdown products. We show that PLA breakdown products are oxidized and may contain aldehydes and/or ketones. The breakdown produces nanosized particles, nanoplastics, and possibly other small molecules as lactide or cyclic oligomers. Further, we show that all PLA breakdown nanoplastics extended the survival rate in Daphnia magna in an acute toxicity assay, however, only PLA plastic cup breakdown nanoplastics showed a significant difference compared to a control group.
  •  
40.
  • Kelpsiene, Egle, et al. (författare)
  • Protein binding on acutely toxic and non-toxic polystyrene nanoparticles during filtration by Daphnia magna
  • 2022
  • Ingår i: Environmental Science: Nano. - : Royal Society of Chemistry (RSC). - 2051-8153 .- 2051-8161.
  • Tidskriftsartikel (refereegranskat)abstract
    • Nanomaterials can adsorb biomolecules to their surface and form a protein corona. Here we investigated the protein profile bound to different sizes of aminated and carboxylated polystyrene (PS) nanoparticles after passing through the digestive tract of the freshwater zooplankter Daphnia magna. We found that acutely toxic aminated 53 nm PS nanoparticles bind a different set of proteins compared to other non-toxic PS nanoparticles. The aminated PS nanoparticles bind a higher number of proteins, which are smaller and more acidic, compared to the proteins which bind to the PS nanoparticles that are non-toxic in acute toxicity tests. The proteins bound to toxic nanoparticles can be divided into two groups. One group of proteins which function is related to the digestive system, whereas the other group of proteins can be related to the epithelium, intracellular structures and processes. Finally, we observed that not only proteins bind to the surfaces of the nanoparticles. Triglycerides effectively bind to 200 nm carboxylated PS nanoparticles but not to the other tested nanoparticles. These results provide information about the composition of the corona formed on surfaces of nanoparticles after a short-term incubation with D. magna and give insights to what underlies the acute toxicity caused by nanoparticles.
  •  
41.
  • Kelpsiene, Egle, et al. (författare)
  • Review of ecotoxicological studies of widely used polystyrene nanoparticles
  • 2022
  • Ingår i: Environmental Science: Processes & Impacts. - 2050-7895. ; 24:1, s. 8-16
  • Forskningsöversikt (refereegranskat)abstract
    • With polystyrene nanoparticles being widely used in various applications, there is a great need for deeper knowledge on the safety, fate and biological effects of these particles on both individual living organisms and the whole ecosystems. Due to this, there is a growing interest in performing ecotoxicological studies using model plastic nanoparticles, and consequently it generates an increasing number of published papers describing the negative impact on wildlife caused by such nanoparticles. Polystyrene is the most studied nanosized plastic, therefore this review focuses on research conducted with manufactured polystyrene nanoparticles. The aim of the present article is to provide a critical methodological outline of the existing ecotoxicological studies on the effects of polystyrene nanoparticles on aquatic organisms. Going through the published articles, we noted that particle characterization especially in the test medium, can be improved. The analysis also highlights the importance of purifying the polystyrene nanoparticles before studying its toxicity. Furthermore, the size characterization of such nanoparticles is underemphasized, and in future studies, authors should consider including more techniques to achieve this goal. Finally, short-term or direct exposure scenarios do not add the most environmentally relevant knowledge in terms of the toxicity caused by polystyrene nanoparticles.
  •  
42.
  • Kelpsiene, Egle, et al. (författare)
  • The effect of natural biomolecules on yttrium oxide nanoparticles from a Daphnia magna survival rate perspective
  • 2023
  • Ingår i: Nanotoxicology. - : Taylor and Francis Ltd.. - 1743-5390 .- 1743-5404. ; 17:4, s. 385-399
  • Tidskriftsartikel (refereegranskat)abstract
    • The attention to rare earth oxide nanoparticles (NPs), including yttrium oxide (Y2O3), has increased in many fields due to their unique structural characteristics and functional properties. The aim of our study was to investigate the mechanisms by which bio-corona formation on Y2O3 NPs affects their environmental fate and toxicity. The Y2O3 NPs induced toxicity to freshwater filter feeder Daphnia magna at particle concentrations of 1 and 10 mg/L, regardless of particle size. Interactions between naturally excreted biomolecules (e.g. protein, lipids, and polysaccharides) derived from D. magna, and the Y2O3 NPs (30–45 nm) resulted in the formation of an eco-corona, which reduced their toxic effects toward D. magna at a particle concentration of 10 mg/L. No effects were observed at lower concentrations or for the other particle sizes investigated. Copper-zinc (Cu-Zn) superoxide dismutase, apolipophorins, and vitellogenin-1 proteins proved to be the most prominent proteins of the adsorbed corona, and possibly a reason for the reduced toxicity of the 30–45 nm Y2O3 NPs toward D. magna.
  •  
43.
  • Khort, Alexander, et al. (författare)
  • Eco-corona-mediated transformation of nano-sized Y2O3 in simulated freshwater : A short-term study
  • 2024
  • Ingår i: NanoImpact. - 2452-0748. ; 33
  • Tidskriftsartikel (refereegranskat)abstract
    • The use of metal and metal oxide nanomaterials (NMs) is experiencing a significant surge in popularity due to their distinctive structures and properties, making them highly attractive for a wide range of applications. This increases the risks of their potential negative impact on organisms if dispersed into the environment. Information about their behavior and transformation upon environmental interactions in aquatic settings is limited. In this study, the influence of naturally excreted biomolecules from the zooplankton Daphnia magna on nanosized Y2O3 of different concentrations was systematically examined in synthetic freshwater in terms of adsorption and eco-corona formation, colloidal stability, transformation, dissolution, and ecotoxicity towards D. magna. The formation of an eco-corona on the surface of the Y2O3 NMs leads to improved colloidal stability and a reduced extent of dissolution. Exposure to the Y2O3 NMs lowered the survival probability of D. magna considerably. The ecotoxic potency was slightly reduced by the formation of the eco-corona, though shown to be particle concentration-specific. Overall, the results highlight the importance of systematic mechanistic and fundamental studies of factors that can affect the environmental fate and ecotoxic potency of NMs.
  •  
44.
  • Lima, Tânia, et al. (författare)
  • Understanding the Lipid and Protein Corona Formation on Different Sized Polymeric Nanoparticles
  • 2020
  • Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10
  • Tidskriftsartikel (refereegranskat)abstract
    • When in contact with biological fluids, nanoparticles dynamically absorb biomolecules like proteins and lipids onto their surface, forming a “corona”. This biocorona is a dynamic and complex structure that determines how host cells respond to nanoparticles. Despite the common use of mouse models in pre-clinical and toxicological experiments, the impact of corona formed in mouse serum on the biophysical and biological properties of different size NP has not been thoroughly explored. Furthering the knowledge on the corona formed on NP exposed to mouse serum proteins can help in understanding what role it might have in in vivo studies at systemic, tissue, and cellular levels. To investigate biocorona formation, different sized polystyrene NP were exposed to mouse serum. Our data show a size- and time-dependent protein and lipid corona formation. Several proteins were identified and apolipoproteins were by far the most common group on the NPs surfaces. Moreover, we observed that cholesterol and triglycerides effectively bind to NP emphasizing that proteins are not the only biomolecules with high-affinity binding to nanomaterial surfaces. These results highlight that further knowledge on NP interactions with mouse serum is necessary regarding the common use of this model to predict the in vivo efficiency of NP.
  •  
45.
  • Lima, Tânia, et al. (författare)
  • β-Glucan-Functionalized Nanoparticles Down-Modulate the Proinflammatory Response of Mononuclear Phagocytes Challenged with Candida albicans
  • 2022
  • Ingår i: Nanomaterials. - : MDPI AG. - 2079-4991. ; 12:14
  • Tidskriftsartikel (refereegranskat)abstract
    • Systemic fungal infections are associated with significant morbidity and mortality, and Candida albicans is the most common causative agent. Recognition of yeast cells by immune cell surface receptors can trigger phagocytosis of fungal pathogens and a pro-inflammatory response that may contribute to fungal elimination. Nevertheless, the elicited inflammatory response may be deleterious to the host by causing excessive tissue damage. We developed a nanoparticle-based approach to modulate the host deleterious inflammatory consequences of fungal infection by using β1,3-glucan-functionalized polystyrene (β-Glc-PS) nanoparticles. β-Glc-PS nanoparticles decreased the levels of the proinflammatory cytokines TNF-α, IL-6, IL-1β and IL-12p40 detected in in vitro culture supernatants of bone marrow-derived dendritic cells and macrophage challenged with C. albicans cells. Moreover, β-Glc-PS nanoparticles impaired the production of reactive oxygen species by bone marrow-derived dendritic cells incubated with C. albicans. This immunomodulatory effect was dependent on the nanoparticle size. Overall, β-Glc-PS nanoparticles reduced the proinflammatory response elicited by fungal cells in mononuclear phagocytes, setting the basis for a targeted therapy aimed at protecting the host by lowering the inflammatory cost of infection.
  •  
46.
  • Lundqvist, Martin, et al. (författare)
  • Rapid and facile purification of apolipoprotein A-I from human plasma using thermoresponsive nanoparticles
  • 2011
  • Ingår i: Journal of Biomaterials and Nanobiotechnology. - : Scientific Research Publishing, Inc.. - 2158-7027 .- 2158-7043. ; 2:3, s. 258-266
  • Tidskriftsartikel (refereegranskat)abstract
    • Nanoparticles can be used to purify proteins from plasma. We report here the purification of apolipoprotein A-I (apoA-I) with high specificity from human plasma using copolymeric nanoparticles. We present an optimized protocol using 50:50 NiPAM:BAM copolymer nanoparticles with thermo-responsive properties as an affinity resin. Repeated pelleting and washing of nanoparticle-captured apoA-I is achieved through temperature cycling. The protein is then eluted using urea followed by an ion exchange step for protein concentration and depletion of nanoparticles
  •  
47.
  • Lundqvist, Martin, et al. (författare)
  • The Evolution of the Protein Corona around Nanoparticles: A Test Study
  • 2011
  • Ingår i: ACS Nano. - : American Chemical Society (ACS). - 1936-086X .- 1936-0851. ; 5:9, s. 7503-7509
  • Tidskriftsartikel (refereegranskat)abstract
    • The importance of the protein corona formed around nanoparticles upon entering a biological fluid has recently been highlighted. This corona is, when sufficiently long-lived, thought to govern the particles' biological fate. However, even this long-lived "hard" corona evolves and re-equilibrates as particles pass from one biological fluid to another, and may be an important feature for long-term fate. Here we show the evolution of the protein corona as a result of transfer of nanopaiticles from one biological fluid (plasma) into another (cytosolic fluid), a simple illustrative model for the uptake of nanoparticles into cells. While no direct comparison can be made to what would happen in, for example, the uptake pathway, the results confirm that significant evolution of the corona occurs in the second biological solution, but that the final corona contains a "fingerprint" of its history. This could be evolved to map the transport pathways utilized by nanoparticles, and eventually to predict nanoparticle fate and behavior.
  •  
48.
  • Lundqvist, Martin, et al. (författare)
  • The nanoparticle protein corona formed in human blood or human blood fractions
  • 2017
  • Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 12:4
  • Tidskriftsartikel (refereegranskat)abstract
    • The protein corona formed around nanoparticles in protein-rich fluids plays an important role for nanoparticle biocompatibility, as found in several studies during the last decade. Biological fluids have complex compositions and the molecular components interact and function together in intricate networks. Therefore, the process to isolate blood or the preparation of blood derivatives may lead to differences in the composition of the identified protein corona around nanoparticles. Here, we show distinct differences in the protein corona formed in whole blood, whole blood with EDTA, plasma, or serum. Furthermore, the ratio between particle surface area to protein concentration influences the detected corona. We also show that the nanoparticle size per se influences the formed protein corona due to curvature effects. These results emphasize the need of investigating the formation and biological importance of the protein corona in the same environment as the nanoparticles are intended for or released into.
  •  
49.
  • Lundqvist, Martin, et al. (författare)
  • Three Decades of Research about the Corona Around Nanoparticles : Lessons Learned and Where to Go Now
  • 2020
  • Ingår i: Small. - : Wiley. - 1613-6810 .- 1613-6829. ; 16:46
  • Tidskriftsartikel (refereegranskat)abstract
    • The research about how a nanoparticle (NP) interacts with a complex biological solution has been conducted, according to the literature, for almost three decades. A significant amount of data has been generated, especially in the last one and a half decade. First, it became its own research field which was later divided into many subresearch fields. This outlook does not aim to be a comprehensive review of the field or any of its subresearch fields. There is too much data published to attempt that. Instead, here it has been tried to highlight what, in the opinion, is the main step taken during these three decades. Thereafter, the weaknesses and end are pointed out with what needs to be the main focus for the future to understand the protein corona formation in the bloodstream, which is a prerequisite for the developing of true target specific drug-delivering nanoparticles.
  •  
50.
  • Lynch, Iseult, et al. (författare)
  • The nanoparticle - protein complex as a biological entity; a complex fluids and surface science challenge for the 21st century
  • 2007
  • Ingår i: Advances in Colloid and Interface Science. - : Elsevier BV. - 1873-3727 .- 0001-8686. ; 134-135, s. 167-174
  • Tidskriftsartikel (refereegranskat)abstract
    • The major aim of our current work is to develop a deep understanding of biological effects of nanoparticles and how these effects are mediated by proteins that are adsorbed on the nanoparticles under different biological circumstances. Due to their small size, nanoparticles have distinct properties compared to the bulk form of the same materials, and these properties are rapidly revolutionizing many areas of medicine and technology. However, relatively little is known about the interaction of nanoscale objects with biological systems, as this requires quite different concepts from more established nanoscience. Thus, we have argued that in a biological fluid, proteins associate with nanoparticles, and it is the amount and presentation of the proteins on the surface rather than the particles themselves that are the cause of numerous biological responses. It is this outer layer of proteins that is seen by the biological cells, and leads to their responses. We are developing novel techniques to identify and quantify the proteins that are consistently associated with nanoparticles, as a function of the nanoparticle size, shape, and surface properties, and to correlate the adsorbed protein identities with their association and dissociation rates to and from the nanoparticles. We also seek to understand the degree of conformational change that they undergo upon adsorption to the nanoparticles. In essence, we wish to create "epitope maps" of the protein corona that surrounds nanoparticles in biological solutions, as it is the particle-protein complex that is the biologically active entity. (c) 2007 Elsevier B.V. All rights reserved.
  •  
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