| 1. |
- Cabaleiro-Lago, Celia, et al.
(författare)
-
Inhibition of Amyloid beta Protein Fibrillation by Polymeric Nanoparticles
- 2008
-
Ingår i: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 1520-5126 .- 0002-7863. ; 130:46, s. 15437-15443
-
Tidskriftsartikel (refereegranskat)abstract
- Copolymeric NiPAM:BAM nanoparticles of varying hydrophobicity were found to retard fibrillation of the Alzheimer's disease-associated amyloid beta protein (A beta). We found that these nanoparticles affect mainly the nucleation step of A beta fibrillation. The elongation step is largely unaffected by the particles, and once the M is nucleated, the fibrillation process occurs with the same rate as in the absence of nanoparticles. The extension of the lag phase for fibrillation of A beta is strongly dependent on both the amount and surface character of the nanoparticles. Surface plasmon resonance studies show that A beta binds to the nanoparticles and provide rate and equilibrium constants for the interaction. Numerical analysis of the kinetic data for fibrillation suggests that binding of monomeric A beta and prefibrillar oligomers to the nanoparticles prevents fibrillation. Moreover, we find that fibrillation of A beta initiated in the absence of nanoparticles can be reversed by addition of nanoparticles up to a particular time point before mature fibrils appear.
|
|
| 2. |
|
|
| 3. |
- 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.
|
|
| 4. |
- Gallagher, William M., et al.
(författare)
-
Molecular basis of cell-biomaterial interaction: Insights gained from transcriptomic and proteomic studies
- 2006
-
Ingår i: Biomaterials. - : Elsevier BV. - 1878-5905 .- 0142-9612. ; 27:35, s. 5871-5882
-
Forskningsöversikt (refereegranskat)abstract
- With the growing interest in clinical interventions that involve medical devices, the role for new biomaterials in modern medicine is currently expanding at a phenomenal rate. Failure of most implant materials stems from an inability to predict and control biological phenomena, such as protein adsorption and cell interaction, resulting in an inappropriate host response to the materials. Contemporary advances in biological investigation are starting to shift focus in the biomaterials field, in particular with the advent of high-throughput methodologies for gene and protein expression profiling. Here, we examine the role that emerging transcriptomic and proteomic technologies could play in relation to biomaterial development and usage. Moreover, a number of studies are highlighted which have utilized such approaches in order to try to create a deeper understanding of cell-biomaterial interactions and, hence, improve our ability to predict and control the biocompatibility of new materials. (c) 2006 Elsevier Ltd. All rights reserved.
|
|
| 5. |
- 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.
|
|
| 6. |
- Lindman, Stina, et al.
(författare)
-
Systematic investigation of the thermodynamics of HSA adsorption to N-iso-propylacrylamide/N-tert-butylacrylamide copolymer nanoparticles. Effects of particle size and hydrophobicity
- 2007
-
Ingår i: Nano Letters. - : American Chemical Society (ACS). - 1530-6992 .- 1530-6984. ; 7:4, s. 914-920
-
Tidskriftsartikel (refereegranskat)abstract
- Nanoparticles in biological fluids almost invariably become coated with proteins that may confer nanomedical and nanotoxicological effects. Understanding these effects requires quantitative measurements using simple systems. Adsorption of HSA to copolymer nanoparticles of varying hydrophobicity and curvature was studied using ITC, yielding stoichiometry, affinity, and enthalpy changes upon binding. The hydrophobicity was controlled via the co-monomer ratio, N-iso-propylacrylamide/N-tert-butylacrylamide. The most hydrophobic particles become fully covered with a single layer of protein, except at high curvature.
|
|
| 7. |
- Linse, Sara, et al.
(författare)
-
Nucleation of protein fibrillation by nanoparticles
- 2007
-
Ingår i: Proceedings of the National Academy of Sciences. - : Proceedings of the National Academy of Sciences. - 1091-6490 .- 0027-8424. ; 104:21, s. 8691-8696
-
Tidskriftsartikel (refereegranskat)abstract
- Nanoparticles present enormous surface areas and are found to enhance the rate of protein fibrillation by decreasing the lag time for nucleation. Protein fibrillation is involved in many human diseases, including Alzheimer's, Creutzfeld-Jacob disease, and dialysis-related amyloidosis. Fibril formation occurs by nucleation-dependent kinetics, wherein formation of a critical nucleus is the key rate-determining step, after which fibrillation proceeds rapidly. We show that nanoparticles (copolymer particles, cerium oxide particles, quantum dots, and carbon nanotubes) enhance the probability of appearance of a critical nucleus for nucleation of protein fibrils from human beta(2)-microglobulin. The observed shorter lag (nucleation) phase depends on the amount and nature of particle surface. There is an exchange of protein between solution and nanoparticle surface, and beta(2)-Microglobulin forms multiple layers on the particle surface, providing a locally increased protein concentration promoting oligomer formation. This and the shortened lag phase suggest a mechanism involving surf ace-assisted nucleation that may increase the risk for toxic cluster and amyloid formation. It also opens the door to new routes for the controlled self-assembly of proteins and peptides into novel nanomaterials.
|
|
| 8. |
- Lynch, Iseult
(författare)
-
Are there generic mechanisms governing interactions between nanoparticles and cells? Epitope mapping the outer layer of the protein-material interface
- 2007
-
Ingår i: Physica A: Statistical Mechanics and its Applications. - : Elsevier BV. - 0378-4371. ; 373, s. 511-520
-
Tidskriftsartikel (refereegranskat)abstract
- In this paper we discuss the possibility of a general paradigm for cell-biomaterial and cell-nanoparticle interactions. The basis of the paradigm is that the nature of the biomaterial or nanoparticle surface is not the important parameter, but rather the nature of the outermost layer of adsorbed proteins as well as long-lived misfolded proteins shed from the surfaces. If the adsorbed protein is irreversibly adsorbed onto the surface it may be sufficiently disrupted so that a variety of peptide units (here termed "cryptic epitopes") not usually expressed in nature at the surface of the protein become exposed. Similarly, where there is a slow exchange time with the surface, surface-induced perturbations may lead to long-lived misfolded proteins being shed from the surface and continuing to express altered surface peptide sequences. In cases where the proteins have lost most of their tertiary structure, anomalous peptide sequences and geometries that are not displayed at the surface by the native protein may in fact be presented after surface adsorption of a protein. Such anomalous surface expressions could contain novel epitopes that trigger various signalling pathways or even diseases. Thus, future approaches to understanding cell-biomaterial and cell-nanoparticle interactions should focus on characterising the outer layer of the adsorbed proteins, or "epitope mapping" as well as examining the possibility of formation of essentially "new" proteins as a result of desorption of conformationally or geometrically altered proteins. (c) 2006 Published by Elsevier B.V.
|
|
| 9. |
- Lynch, Iseult, et al.
(författare)
-
Correlation of the adhesive properties of cells to N-isopropylacrylamide/N-tert-butylacrylamide copolymer surfaces with changes in surface structure using contact angle measurements, molecular simulations, and Raman spectroscopy
- 2005
-
Ingår i: Chemistry of Materials. - : American Chemical Society (ACS). - 0897-4756 .- 1520-5002. ; 17:15, s. 3889-3898
-
Tidskriftsartikel (refereegranskat)abstract
- A series of copolymers of N-isopropylacrylamide (NIPAM) and the more hydrophobic comonomer N-tert-butylacrylamide (NTBAM), with increasing NTBAM content (i.e., increasing hydrophobicity) were prepared. The adhesion of human epithelial cells on polymer films prepared from copolymers of NIPAM: NTBAM was observed to increase with increasing polymer hydrophobicity. However, in the absence of serum, cell adhesion to the different surfaces was statistically indistinguishable. Thus, it appears that the copolymer films differentially support cell adhesion due to selective adsorption of proteins from the physiological environment (the serum). Using contact angle measurements, molecular simulations, and Raman spectroscopy to characterize the different surfaces, we show evidence that the different behavior of cells on the films of increasing hydrophobicity is actually due to the different chemical properties of the surfaces with increasing content of NTBAM in the copolymers. As the NTBAM content is increased, the number of NH residues at the surface decreases, due to the additional steric hindrance of the bulkier NTBAM group, which results in decreased hydrogen bonding and thus decreased adsorption of proteins such as albumin. However, in some cases, the adsorption is driven by hydrophobic interactions, and proteins such as fibronectin were found to adsorb more to the films with a higher content of NTBAM. There appears, thus, to be a direct correlation between surface composition, i.e., the functional groups exposed at the surface, and protein binding and subsequent cell adhesion.
|
|
| 10. |
- Lynch, Iseult, et al.
(författare)
-
Hydrophobicity and counterion effects on the binding of ionic surfactants to uncharged polymeric hydrogels
- 2005
-
Ingår i: The Journal of Physical Chemistry Part B. - : American Chemical Society (ACS). - 1520-5207 .- 1520-6106. ; 109:9, s. 4252-4257
-
Tidskriftsartikel (refereegranskat)abstract
- Gel swelling experiments have been used to study the binding of ionic surfactants to a series of nonionic alkylacrylamide hydrogels of increasing hydrophobicity. The binding of hexadecyl trimethylammonium (C-16-TA(+)) to uncharged gels is sensitive to both the hydrophobicity of the gel and the counterion to the surfactant. There is a minimum hydrophobicity threshold below which binding of the surfactant does not occur, and this is influenced by the counterion to the surfactant. The surfactant concentration at the onset of binding, the critical association concentration (cac), decreases with increasing gel hydrophobicity. The maximum swelling of the gel (at intermediate network hydrophobicity) increases in the order of the Hofmeister series of anions, bromide (Br-) < chloride (Cl-) < acetate (Ac-). At higher gel hydrophobicity, differences in swelling are no longer observed on changing the counterion. A minimum hydrophobicity threshold was also found for the binding of the anionic surfactants sodium dodecyl sulfate (SDS) and sodium dodecyl-di(ethylene oxide)sulfate (SD-(EO)(2)-S). Differences in the swelling behavior with network hydrophobicity are explained in terms of the degree of saturation of the gel with surfactant at the cmc.
|
|
