| 1. |
- Cabaleiro-Lago, Celia, et al.
(författare)
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Inhibition of IAPP and IAPP(20-29) fibrillation by polymeric nanoparticles
- 2010
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Ingår i: Langmuir. - : The American Chemical Society (ACS). - 0743-7463 .- 1520-5827. ; 26:5, s. 3453-3461
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Tidskriftsartikel (refereegranskat)abstract
- The fibrillation process of the islet amyloid polypeptide (IAPP) and its fragment (IAPP(20-29)) was studied by means of Thioflavin T (ThT) fluorescence and transmission electron microscopy in the absence and presence of N-isopropylacrylamide:N-tert-butylacrylamide (NiPAM:BAM) copolymeric nanoparticles. The process was found to be strongly affected by the presence of the nanoparticles, which retard protein fibrillation as a function of the chemical surface properties of the nanoparticles. The NiPAM:BAM ratio was varied from 50:50 to 100:0. The nanoparticles with higher fraction of NiPAM imposed the strongest retardation of IAPP and IAPP(20-29) fibrillation. These particles have the strongest hydrogen bonding capacity due to the less bulky N-isopropyl group and thus less steric hindrance of the hydrogen-bonding groups of the nanoparticle polymer backbone. Kinetic fibrillation data, as monitored by ThT fluorescence and supported by surface plasmon resonance experiments, suggest that the peptide is strongly absorbed onto the surface of the nanoparticles. This interaction reduces the concentration of peptide free in solution available to proceed to fibrillation which results in an increased lag time of fibrillation, observed as a delayed onset of ThT fluorescence increase, plus a reduction of the amount of fibrils formed as indicated by the equilibrium values at the end of the fibrillation reaction. For the fragment (IAPP(20-29)), the presence of nanoparticles changes the mechanism of association from monomers to fibrils, by interfering with early oligomeric species along the fibrillation pathway.
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| 2. |
- Aslund, Ingrid, et al.
(författare)
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Diffusion NMR for determining the homogeneous length-scale in lamellar phases.
- 2008
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Ingår i: Journal of Physical Chemistry B. - : The American Chemical Society (ACS). - 1520-6106 .- 1520-5207. ; 112:10, s. 2782-2794
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Tidskriftsartikel (refereegranskat)abstract
- The size of the anisotropic domains in a lyotropic liquid crystal is estimated using a new protocol for diffusion NMR. Echo attenuation decays are recorded for different durations of the displacement-encoding gradient pulses, while keeping the effective diffusion time and the range of the wave vectors constant. Deviations between the sets of data appear if there are non-Gaussian diffusion processes occurring on the time-scale defined by the gradient pulse duration and the length-scale defined by the wave vector. The homogeneous length-scale is defined as the minimum length-scale for which the diffusion appears to be Gaussian. Simulations are performed to show that spatial variation of the director orientation in an otherwise homogeneous system is sufficient to induce non-Gaussian diffusion. The method is demonstrated by numerical solutions of the Bloch-Torrey equation and experiments on a range of lamellar liquid crystals with different domain sizes.
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| 3. |
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| 4. |
- Assarsson, Anna, et al.
(författare)
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Charge dependent retardation of amyloid β aggregation by hydrophilic proteins
- 2014
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Ingår i: ACS Chemical Neuroscience. - 1948-7193 .- 1948-7193. ; 5:4, s. 266-74
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Tidskriftsartikel (refereegranskat)abstract
- The aggregation of amyloid β peptides (Aβ) into amyloid fibrils is implicated in the pathology of Alzheimer's disease. In light of the increasing number of proteins reported to retard Aβ fibril formation, we investigated the influence of small hydrophilic model proteins of different charge on Aβ aggregation kinetics and their interaction with Aβ. We followed the amyloid fibril formation of Aβ40 and Aβ42 using thioflavin T fluorescence in the presence of six charge variants of calbindin D9k and single-chain monellin. The formation of fibrils was verified with transmission electron microscopy. We observe retardation of the aggregation process from proteins with net charge +8, +2, -2, and -4, whereas no effect is observed for proteins with net charge of -6 and -8. The single-chain monellin mutant with the highest net charge, scMN+8, has the largest retarding effect on the amyloid fibril formation process, which is noticeably delayed at as low as a 0.01:1 scMN+8 to Aβ40 molar ratio. scMN+8 is also the mutant with the fastest association to Aβ40 as detected by surface plasmon resonance, although all retarding variants of calbindin D9k and single-chain monellin bind to Aβ40.
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| 5. |
- Assarsson, Anna, et al.
(författare)
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Effects of polyamino acids and polyelectrolytes on amyloid β fibril formation
- 2014
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Ingår i: Langmuir. - : The American Chemical Society (ACS). - 0743-7463 .- 1520-5827. ; 30:29, s. 8812-8
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Tidskriftsartikel (refereegranskat)abstract
- The fibril formation of the neurodegenerative peptide amyloid β (Aβ42) is sensitive to solution conditions, and several proteins and peptides have been found to retard the process. Aβ42 fibril formation was followed with ThT fluorescence in the presence of polyamino acids (poly-glutamic acid, poly-lysine, and poly-threonine) and other polymers (poly(acrylic acid), poly(ethylenimine), and poly(diallyldimethylammonium chloride). An accelerating effect on the Aβ42 aggregation process is observed from all positively charged polymers, while no effect is seen from the negative or neutral polymers. The accelerating effect is dependent on the concentration of positive polymer in a highly reproducible manner. Acceleration is observed from a 1:500 polymer to Aβ42 weight ratio and up. Polyamino acids and the other polymers exert quantitatively the same effect at the same concentrations based on weight. Fibrils are formed in all cases as verified by transmission electron microscopy. The concentrations of polymers required for acceleration are too low to affect the Aβ42 aggregation process through increased ionic strength or molecular crowding effects. Instead, the acceleration seems to arise from the locally increased Aβ42 concentration near the polymers, which favors association and affects the electrostatic environment of the peptide.
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| 6. |
- Assarsson, Anna, et al.
(författare)
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Effects of Polyamino Acids and Polyelectrolytes on Amyloid β Fibril Formation.
- 2014
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Ingår i: Langmuir. - : American Chemical Society (ACS). - 0743-7463 .- 1520-5827. ; 30:29, s. 8812-8818
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Tidskriftsartikel (refereegranskat)abstract
- The fibril formation of the neurodegenerative peptide amyloid β (Aβ42) is sensitive to solution conditions, and several proteins and peptides have been found to retard the process. Aβ42 fibril formation was followed with ThT fluorescence in the presence of polyamino acids (poly-glutamic acid, poly-lysine, and poly-threonine) and other polymers (poly(acrylic acid), poly(ethylenimine), and poly(diallyldimethylammonium chloride). An accelerating effect on the Aβ42 aggregation process is observed from all positively charged polymers, while no effect is seen from the negative or neutral polymers. The accelerating effect is dependent on the concentration of positive polymer in a highly reproducible manner. Acceleration is observed from a 1:500 polymer to Aβ42 weight ratio and up. Polyamino acids and the other polymers exert quantitatively the same effect at the same concentrations based on weight. Fibrils are formed in all cases as verified by transmission electron microscopy. The concentrations of polymers required for acceleration are too low to affect the Aβ42 aggregation process through increased ionic strength or molecular crowding effects. Instead, the acceleration seems to arise from the locally increased Aβ42 concentration near the polymers, which favors association and affects the electrostatic environment of the peptide.
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| 7. |
- Assarsson, Anna, et al.
(författare)
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Inactivation and adsorption of human carbonic anhydrase II by nanoparticles
- 2014
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Ingår i: Langmuir. - : The American Chemical Society (ACS). - 0743-7463 .- 1520-5827. ; 30:31, s. 9448-56
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Tidskriftsartikel (refereegranskat)abstract
- The enzymatic activity of human carbonic anhydrase II (HCAII) was studied in the presence of nanoparticles of different nature and charge. Negatively charged nanoparticles inhibit HCAII whereas no effect is seen for positively charged particles. The kinetic effects were correlated with the strength of binding of the enzyme to the particle surface as measured by ITC and adsorption assays. Moreover, conformational changes upon adsorption were observed by circular dichroism. The main initial driving force for the adsorption of HCAII to nanoparticles is of electrostatic nature whereas the hydrophobic effect is not strong enough to drive the initial binding. This is corroborated by the fact that HCAII do not adsorb on positively charged hydrophobic polystyrene nanoparticles. Furthermore, the dehydration of the particle and protein surface seems to play an important role in the inactivation of HCAII by carboxyl-modified polystyrene nanoparticles. On the other hand, the inactivation by unmodified polystyrene nanoparticles is mainly driven by intramolecular interactions established between the protein and the nanoparticle surface upon conformational changes in the protein.
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| 8. |
- Assarsson, Anna, et al.
(författare)
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Inactivation and Adsorption of Human Carbonic Anhydrase II by Nanoparticles.
- 2014
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Ingår i: Langmuir. - : American Chemical Society (ACS). - 0743-7463 .- 1520-5827. ; 30:31, s. 9448-9456
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Tidskriftsartikel (refereegranskat)abstract
- The enzymatic activity of human carbonic anhydrase II (HCAII) was studied in the presence of nanoparticles of different nature and charge. Negatively charged nanoparticles inhibit HCAII whereas no effect is seen for positively charged particles. The kinetic effects were correlated with the strength of binding of the enzyme to the particle surface as measured by ITC and adsorption assays. Moreover, conformational changes upon adsorption were observed by circular dichroism. The main initial driving force for the adsorption of HCAII to nanoparticles is of electrostatic nature whereas the hydrophobic effect is not strong enough to drive the initial binding. This is corroborated by the fact that HCAII do not adsorb on positively charged hydrophobic polystyrene nanoparticles. Furthermore, the dehydration of the particle and protein surface seems to play an important role in the inactivation of HCAII by carboxyl-modified polystyrene nanoparticles. On the other hand, the inactivation by unmodified polystyrene nanoparticles is mainly driven by intramolecular interactions established between the protein and the nanoparticle surface upon conformational changes in the protein.
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| 9. |
- Cabaleiro-Lago, Celia, et al.
(författare)
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Characterization of alkane diol-CD complexes. Acid denitrosation of N-methyl-N-nitroso-p-toluenesulphonamide as a chemical probe
- 2006
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Ingår i: JOURNAL OF INCLUSION PHENOMENA AND MACROCYCLIC CHEMISTRY. - Univ Vigo, Dept Quim Fis, Vigo 36200, Spain. Univ Santiago de Compostela, Dept Quim Fis, Santiago De Compostela 15706, Spain. : SPRINGER. - 1388-3127. ; 54:3-4, s. 209-216
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Tidskriftsartikel (refereegranskat)abstract
- A study was carried out on the acid denitrosation of N-methyl-N-nitroso-p-toluenesulfonamide (MNTS) in mixed systems made up of linear (geminal and terminal) alkyl diols and beta-cyclodextrin (CD). The alkyl diols used allowed us to vary the length of the hydrocarbon chain from 2 to 6 carbon atoms. The observed rate constant, k(obs), decreases in the presence of CD. The inhibition profile decreases as the as the number of carbons in the chain is increased. This behaviour can be interpreted as a consequence of a balance between the complexation processes of MNTS and the alkyl diols by the CD. At a constant CD concentration and increase in the diols concentration decreases the concentration of free cyclodextrin available to complex with MNTS molecules and therefore produces an increases in the observed rate constant. The results were interpreted in terms of two different models; trough the presupposition and non-presupposition of a stoichiometry for the CD-diols complex. Both models agreed quite well and allow us to determine the uncomplexed cyclodextrin concentration in each case as well as the stoichiometry of the complexes. The binding constant for both types of alkane diols increase with increasing the number of carbon in the chain. Besides, the binding constant of the alpha,beta-alkane diols is higher than for the analog alpha,beta-alkane diols. One of the main consequences of this study is that the acid denitrosation of MNTS can be use to obtain the stochiometry of the CD-diol complexes and to monitor the free cyclodextrin concentration.
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| 10. |
- Cabaleiro-Lago, Celia, et al.
(författare)
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Dual Effect of Amino Modified Polystyrene Nanoparticles on Amyloid beta Protein Fibrillation
- 2010
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Ingår i: ACS Chemical Neuroscience. - : American Chemical Society (ACS). - 1948-7193. ; 1:4, s. 279-287
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Tidskriftsartikel (refereegranskat)abstract
- The fibrillation kinetics of the amyloid beta peptide is analyzed in presence of cationic polystyrene nanoparticles of different size. The results highlight the importance of the ratio between the peptide and particle concentration. Depending on the specific ratio, the kinetic effects vary from acceleration of the fibrillation process by reducing the lag phase at low particle surface area in solution to inhibition of the fibrillation process at high particle surface area. The kinetic behavior can be explained if we assume a balance between two different pathways: first fibrillation of free monomer in solution and second nucleation and fibrillation promoted at the particle surface. The overall rate of fibrillation will depend on the interplay between these two pathways, and the predominance of one mechanism over the other will be determined by the relative equilibrium and rate constants.
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