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Publications (10 of 84) Show all publications
Baronio, C. M. & Barth, A. (2024). Refining protein amide I spectrum simulations with simple yet effective electrostatic models for local wavenumbers and dipole derivative magnitudes. Physical Chemistry, Chemical Physics - PCCP, 26(2), 1166-1181
Open this publication in new window or tab >>Refining protein amide I spectrum simulations with simple yet effective electrostatic models for local wavenumbers and dipole derivative magnitudes
2024 (English)In: Physical Chemistry, Chemical Physics - PCCP, ISSN 1463-9076, E-ISSN 1463-9084, Vol. 26, no 2, p. 1166-1181Article in journal (Refereed) Published
Abstract [en]

Analysis of the amide I band of proteins is probably the most wide-spread application of bioanalytical infrared spectroscopy. Although highly desirable for a more detailed structural interpretation, a quantitative description of this absorption band is still difficult. This work optimized several electrostatic models with the aim to reproduce the effect of the protein environment on the intrinsic wavenumber of a local amide I oscillator. We considered the main secondary structures – α-helices, parallel and antiparallel β-sheets – with a maximum of 21 amide groups. The models were based on the electric potential and/or the electric field component along the CO bond at up to four atoms in an amide group. They were bench-marked by comparison to Hessian matrices reconstructed from density functional theory calculations at the BPW91, 6-31G** level. The performance of the electrostatic models depended on the charge set used to calculate the electric field and potential. Gromos and DSSP charge sets, used in common force fields, were not optimal for the better performing models. A good compromise between performance and the stability of model parameters was achieved by a model that considered the electric field at the positions of the oxygen, nitrogen, and hydrogen atoms of the considered amide group. The model describes also some aspects of the local conformation effect and performs similar on its own as in combination with an explicit implementation of the local conformation effect. It is better than a combination of a local hydrogen bonding model with the local conformation effect. Even though the short-range hydrogen bonding model performs worse, it captures important aspects of the local wavenumber sensitivity to the molecular surroundings. We improved also the description of the coupling between local amide I oscillators by developing an electrostatic model for the dependency of the dipole derivative magnitude on the protein environment.

National Category
Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:su:diva-225541 (URN)10.1039/d3cp02018e (DOI)001125291900001 ()38099625 (PubMedID)2-s2.0-85180120792 (Scopus ID)
Available from: 2024-01-17 Created: 2024-01-17 Last updated: 2024-01-17Bibliographically approved
Paul, S., Jenistova, A., Vosough, F., Berntsson, E., Mörman, C., Jarvet, J., . . . Barth, A. (2023). 13C- and 15N-labeling of amyloid-β and inhibitory peptides to study their interaction via nanoscale infrared spectroscopy. Communications Chemistry, 6(1), Article ID 163.
Open this publication in new window or tab >>13C- and 15N-labeling of amyloid-β and inhibitory peptides to study their interaction via nanoscale infrared spectroscopy
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2023 (English)In: Communications Chemistry, E-ISSN 2399-3669, Vol. 6, no 1, article id 163Article in journal (Refereed) Published
Abstract [en]

Interactions between molecules are fundamental in biology. They occur also between amyloidogenic peptides or proteins that are associated with different amyloid diseases, which makes it important to study the mutual influence of two polypeptides on each other's properties in mixed samples. However, addressing this research question with imaging techniques faces the challenge to distinguish different polypeptides without adding artificial probes for detection. Here, we show that nanoscale infrared spectroscopy in combination with C-13, N-15-labeling solves this problem. We studied aggregated amyloid-& beta; peptide (A & beta;) and its interaction with an inhibitory peptide (NCAM1-PrP) using scattering-type scanning near-field optical microscopy. Although having similar secondary structure, labeled and unlabeled peptides could be distinguished by comparing optical phase images taken at wavenumbers characteristic for either the labeled or the unlabeled peptide. NCAM1-PrP seems to be able to associate with or to dissolve existing A & beta; fibrils because pure A & beta; fibrils were not detected after mixing. Interactions of proteins or polypeptides with different secondary structures can be studied in a mixture by nanoscale infrared spectroscopy, however, this technique remains challenging for polypeptides with similar secondary structures. Here, the authors demonstrate clear discrimination of two polypeptides from a mixture by scattering-type scanning near-field optical microscopy when one of the components is labeled with C-13- and N-15-isotopes.

National Category
Chemical Sciences Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:su:diva-221129 (URN)10.1038/s42004-023-00955-w (DOI)001042052900001 ()37537303 (PubMedID)2-s2.0-85167397298 (Scopus ID)
Available from: 2023-09-18 Created: 2023-09-18 Last updated: 2023-09-18Bibliographically approved
Berntsson, E., Vosough, F., Noormagi, A., Padari, K., Asplund, F., Gielnik, M., . . . Wärmländer, S. (2023). Characterization of Uranyl (UO22+) Ion Binding to Amyloid Beta (Aβ) Peptides: Effects on Aβ Structure and Aggregation. ACS Chemical Neuroscience, 14(15), 2618-2633
Open this publication in new window or tab >>Characterization of Uranyl (UO22+) Ion Binding to Amyloid Beta (Aβ) Peptides: Effects on Aβ Structure and Aggregation
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2023 (English)In: ACS Chemical Neuroscience, E-ISSN 1948-7193, Vol. 14, no 15, p. 2618-2633Article in journal (Refereed) Published
Abstract [en]

Uranium (U) is naturally present in ambient air, water, and soil, and depleted uranium (DU) is released into the environment via industrial and military activities. While the radiological damage from U is rather well understood, less is known about the chemical damage mechanisms, which dominate in DU. Heavy metal exposure is associated with numerous health conditions, including Alzheimer’s disease (AD), the most prevalent age-related cause of dementia. The pathological hallmark of AD is the deposition of amyloid plaques, consisting mainly of amyloid-β (Aβ) peptides aggregated into amyloid fibrils in the brain. However, the toxic species in AD are likely oligomeric Aβ aggregates. Exposure to heavy metals such as Cd, Hg, Mn, and Pb is known to increase Aβ production, and these metals bind to Aβ peptides and modulate their aggregation. The possible effects of U in AD pathology have been sparsely studied. Here, we use biophysical techniques to study in vitro interactions between Aβ peptides and uranyl ions, UO22+, of DU. We show for the first time that uranyl ions bind to Aβ peptides with affinities in the micromolar range, induce structural changes in Aβ monomers and oligomers, and inhibit Aβ fibrillization. This suggests a possible link between AD and U exposure, which could be further explored by cell, animal, and epidemiological studies. General toxic mechanisms of uranyl ions could be modulation of protein folding, misfolding, and aggregation. 

Keywords
Alzheimer's disease, amyloid aggregation, metal-protein binding, neurodegeneration, heavy metal toxicity
National Category
Neurosciences Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:su:diva-221233 (URN)10.1021/acschemneuro.3c00130 (DOI)001035034000001 ()37487115 (PubMedID)2-s2.0-85166386170 (Scopus ID)
Available from: 2023-09-19 Created: 2023-09-19 Last updated: 2023-09-19Bibliographically approved
Jafari, M. J., Backlund, F. G., Arndt, T., Schmuck, B., Greco, G., Rising, A., . . . Ederth, T. (2023). Force-Induced Structural Changes in Spider Silk Fibers Introduced by ATR-FTIR Spectroscopy. ACS applied polymer materials, 5(11), 9433-9444
Open this publication in new window or tab >>Force-Induced Structural Changes in Spider Silk Fibers Introduced by ATR-FTIR Spectroscopy
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2023 (English)In: ACS applied polymer materials, ISSN 2637-6105, Vol. 5, no 11, p. 9433-9444Article in journal (Refereed) Published
Abstract [en]

Silk fibers have unique mechanical properties, and many studies of silk aim at understanding how these properties are related to secondary structure content, which often is determined by infrared spectroscopy. We report significant method-induced irreversible structural changes to both natural and synthetic spider silk fibers, derived from the widely used attenuated total reflection Fourier-transform infrared (ATR-FTIR) technique. By varying the force used to bring fibers into contact with the internal reflection elements of ATR-FTIR accessories, we observed correlated and largely irreversible changes in the secondary structure, with shape relaxation under pressure occurring within minutes. Fitting of spectral components shows that these changes agree with transformations from the alpha-helix to the beta-sheet secondary structure with possible contributions from other secondary structure elements. We further confirm the findings with IR microspectroscopy, where similar differences were seen between the pressed and unaffected regions of spider silk fibers. Our findings show that ATR-FTIR spectroscopy requires care in its use and in the interpretation of the results.

Keywords
silk fibers, ATR-FTIR, secondarystructure, pressure effects, spider silk, NT2RepCT minispidroin
National Category
Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:su:diva-224250 (URN)10.1021/acsapm.3c01892 (DOI)001098410600001 ()2-s2.0-85177765433 (Scopus ID)
Available from: 2023-12-06 Created: 2023-12-06 Last updated: 2023-12-06Bibliographically approved
Berntsson, E., Vosough, F., Svantesson, T., Pansieri, J., Iashchishyn, I. A., Ostojic, L., . . . Wärmländer, S. (2023). Residue-specific binding of Ni(II) ions influences the structure and aggregation of amyloid beta (Aβ) peptides. Scientific Reports, 13(1), Article ID 3341.
Open this publication in new window or tab >>Residue-specific binding of Ni(II) ions influences the structure and aggregation of amyloid beta (Aβ) peptides
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2023 (English)In: Scientific Reports, E-ISSN 2045-2322, Vol. 13, no 1, article id 3341Article in journal (Refereed) Published
Abstract [en]

Alzheimer's disease (AD) is the most common cause of dementia worldwide. AD brains display deposits of insoluble amyloid plaques consisting mainly of aggregated amyloid-beta (A beta) peptides, and A beta oligomers are likely a toxic species in AD pathology. AD patients display altered metal homeostasis, and AD plaques show elevated concentrations of metals such as Cu, Fe, and Zn. Yet, the metal chemistry in AD pathology remains unclear. Ni(II) ions are known to interact with A beta peptides, but the nature and effects of such interactions are unknown. Here, we use numerous biophysical methods-mainly spectroscopy and imaging techniques-to characterize A beta/Ni(II) interactions in vitro, for different A beta variants: A beta(1-40), A beta(1-40)(H6A, H13A, H14A), A beta(4-40), and A beta(1-42). We show for the first time that Ni(II) ions display specific binding to the N-terminal segment of full-length A beta monomers. Equimolar amounts of Ni(II) ions retard A beta aggregation and direct it towards non-structured aggregates. The His6, His13, and His14 residues are implicated as binding ligands, and the Ni(II)center dot A beta binding affinity is in the low mu M range. The redox-active Ni(II) ions induce formation of dityrosine cross-links via redox chemistry, thereby creating covalent A beta dimers. In aqueous buffer Ni(II) ions promote formation of beta sheet structure in A beta monomers, while in a membrane-mimicking environment (SDS micelles) coil-coil helix interactions appear to be induced. For SDS-stabilized A beta oligomers, Ni(II) ions direct the oligomers towards larger sizes and more diverse (heterogeneous) populations. All of these structural rearrangements may be relevant for the A beta aggregation processes that are involved in AD brain pathology.

National Category
Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:su:diva-229707 (URN)10.1038/s41598-023-29901-5 (DOI)000986236800026 ()36849796 (PubMedID)
Available from: 2024-05-29 Created: 2024-05-29 Last updated: 2024-05-29Bibliographically approved
Arndt, T., Greco, G., Schmuck, B., Bunz, J., Shilkova, O., Francis, J., . . . Rising, A. (2022). Engineered Spider Silk Proteins for Biomimetic Spinning of Fibers with Toughness Equal to Dragline Silks. Advanced Functional Materials, 32(23), Article ID 2200986.
Open this publication in new window or tab >>Engineered Spider Silk Proteins for Biomimetic Spinning of Fibers with Toughness Equal to Dragline Silks
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2022 (English)In: Advanced Functional Materials, ISSN 1616-301X, E-ISSN 1616-3028, Vol. 32, no 23, article id 2200986Article in journal (Refereed) Published
Abstract [en]

Spider silk is the toughest fiber found in nature, and bulk production of artificial spider silk that matches its mechanical properties remains elusive. Development of miniature spider silk proteins (mini-spidroins) has made large-scale fiber production economically feasible, but the fibers’ mechanical properties are inferior to native silk. The spider silk fiber's tensile strength is conferred by poly-alanine stretches that are zipped together by tight side chain packing in β-sheet crystals. Spidroins are secreted so they must be void of long stretches of hydrophobic residues, since such segments get inserted into the endoplasmic reticulum membrane. At the same time, hydrophobic residues have high β-strand propensity and can mediate tight inter-β-sheet interactions, features that are attractive for generation of strong artificial silks. Protein production in prokaryotes can circumvent biological laws that spiders, being eukaryotic organisms, must obey, and the authors thus design mini-spidroins that are predicted to more avidly form stronger β-sheets than the wildtype protein. Biomimetic spinning of the engineered mini-spidroins indeed results in fibers with increased tensile strength and two fiber types display toughness equal to native dragline silks. Bioreactor expression and purification result in a protein yield of ≈9 g L−1 which is in line with requirements for economically feasible bulk scale production.

Keywords
biomimetic materials, biomimetic spider silk fibers, fibers, protein engineering, recombinant protein production
National Category
Biological Sciences
Identifiers
urn:nbn:se:su:diva-203468 (URN)10.1002/adfm.202200986 (DOI)000772739600001 ()2-s2.0-85127221136 (Scopus ID)
Available from: 2022-04-04 Created: 2022-04-04 Last updated: 2022-06-08Bibliographically approved
Eliaz, D., Paul, S., Benyamin, D., Cernescu, A., Cohen, S. R., Rosenhek-Goldian, I., . . . Shimanovich, U. (2022). Micro and nano-scale compartments guide the structural transition of silk protein monomers into silk fibers. Nature Communications, 13(1), Article ID 7856.
Open this publication in new window or tab >>Micro and nano-scale compartments guide the structural transition of silk protein monomers into silk fibers
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2022 (English)In: Nature Communications, E-ISSN 2041-1723, Vol. 13, no 1, article id 7856Article in journal (Refereed) Published
Abstract [en]

Silk is a unique, remarkably strong biomaterial made of simple protein building blocks. To date, no synthetic method has come close to reproducing the properties of natural silk, due to the complexity and insufficient understanding of the mechanism of the silk fiber formation. Here, we use a combination of bulk analytical techniques and nanoscale analytical methods, including nano-infrared spectroscopy coupled with atomic force microscopy, to probe the structural characteristics directly, transitions, and evolution of the associated mechanical properties of silk protein species corresponding to the supramolecular phase states inside the silkworm's silk gland. We found that the key step in silk-fiber production is the formation of nanoscale compartments that guide the structural transition of proteins from their native fold into crystalline beta-sheets. Remarkably, this process is reversible. Such reversibility enables the remodeling of the final mechanical characteristics of silk materials. These results open a new route for tailoring silk processing for a wide range of new material formats by controlling the structural transitions and self-assembly of the silk protein's supramolecular phases.

National Category
Other Natural Sciences Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:su:diva-230164 (URN)10.1038/s41467-022-35505-w (DOI)001028170500013 ()36543800 (PubMedID)2-s2.0-85144515051 (Scopus ID)
Available from: 2024-06-05 Created: 2024-06-05 Last updated: 2024-06-05Bibliographically approved
Wei, X.-F., Hedenqvist, M. S., Zhao, L., Barth, A. & Yin, H. (2022). Risk for the release of an enormous amount of nanoplastics and microplastics from partially biodegradable polymer blends. Green Chemistry, 24(22), 8742-8750
Open this publication in new window or tab >>Risk for the release of an enormous amount of nanoplastics and microplastics from partially biodegradable polymer blends
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2022 (English)In: Green Chemistry, ISSN 1463-9262, E-ISSN 1463-9270, Vol. 24, no 22, p. 8742-8750Article in journal (Refereed) Published
Abstract [en]

Nanoplastics and microplastics (NMPs) in natural environments are an emerging global concern and understanding their formation processes from macro-plastic items during degradation/weathering is critical for predicting their quantities and impacts in different ecological systems. Here, we show the risk of enormous emissions of NMPs from polymer blends, a source that has not been specifically studied, by taking immiscible (most common case) partially biodegradable polymer blends as an example. The blends have the common “sea-island” morphology, where the minor non-biodegradable polymer phase (polyethylene and polypropylene) is dispersed as NMP particles in the major continuous biodegradable matrix (poly(ϵ-caprolactone)). The dispersed NMP particles with spherical and rod-like shapes are gradually liberated and released to the surrounding aquatic environment during the biodegradation of the matrix polymer. Strikingly, the number of released NMPs from the blend is very high. The blend film surface erosion process, induced by enzymatic hydrolysis of the matrix, involving fragmentation, hole formation, and hole wall detachment, was systematically investigated to reveal the NMP release process. Our findings present direct evidence and detailed insights into the high risk of emissions of NMPs from partially biodegradable immiscible polymer blends with a widespread “sea-island” morphology. Efforts from authorities, developers, manufacturers, and the public are needed to avoid the use of non-biodegradable polymers in blends with biodegradable polymers. 

National Category
Polymer Chemistry
Identifiers
urn:nbn:se:su:diva-212285 (URN)10.1039/d2gc02388a (DOI)2-s2.0-85141761825 (Scopus ID)
Available from: 2022-12-08 Created: 2022-12-08 Last updated: 2022-12-08Bibliographically approved
Arndt, T., Jaudzems, K., Shilkova, O., Francis, J., Johansson, M., Laity, P. R., . . . Rising, A. (2022). Spidroin N-terminal domain forms amyloid-like fibril based hydrogels and provides a protein immobilization platform. Nature Communications, 13, Article ID 4695.
Open this publication in new window or tab >>Spidroin N-terminal domain forms amyloid-like fibril based hydrogels and provides a protein immobilization platform
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2022 (English)In: Nature Communications, E-ISSN 2041-1723, Vol. 13, article id 4695Article in journal (Refereed) Published
Abstract [en]

Recombinant spider silk proteins (spidroins) have multiple potential applications in development of novel biomaterials, but their multimodal and aggregation-prone nature have complicated production and straightforward applications. Here, we report that recombinant miniature spidroins, and importantly also the N-terminal domain (NT) on its own, rapidly form self-supporting and transparent hydrogels at 37 °C. The gelation is caused by NT α-helix to β-sheet conversion and formation of amyloid-like fibrils, and fusion proteins composed of NT and green fluorescent protein or purine nucleoside phosphorylase form hydrogels with intact functions of the fusion moieties. Our findings demonstrate that recombinant NT and fusion proteins give high expression yields and bestow attractive properties to hydrogels, e.g., transparency, cross-linker free gelation and straightforward immobilization of active proteins at high density.

National Category
Biological Sciences
Identifiers
urn:nbn:se:su:diva-209425 (URN)10.1038/s41467-022-32093-7 (DOI)000840984400033 ()35970823 (PubMedID)2-s2.0-85136024394 (Scopus ID)
Available from: 2022-09-20 Created: 2022-09-20 Last updated: 2023-03-28Bibliographically approved
Vosough, F. & Barth, A. (2021). Characterization of Homogeneous and Heterogeneous Amyloid-beta 42 Oligomer Preparations with Biochemical Methods and Infrared Spectroscopy Reveals a Correlation between Infrared Spectrum and Oligomer Size. ACS Chemical Neuroscience, 12(3), 473-488
Open this publication in new window or tab >>Characterization of Homogeneous and Heterogeneous Amyloid-beta 42 Oligomer Preparations with Biochemical Methods and Infrared Spectroscopy Reveals a Correlation between Infrared Spectrum and Oligomer Size
2021 (English)In: ACS Chemical Neuroscience, E-ISSN 1948-7193, Vol. 12, no 3, p. 473-488Article in journal (Refereed) Published
Abstract [en]

Soluble oligomers of the amyloid-β(1-42) (Aβ42) peptide, widely considered to be among the relevant neurotoxic species involved in Alzheimer’s disease, were characterized with a combination of biochemical and biophysical methods. Homogeneous and stable Aβ42 oligomers were prepared by treating monomeric solutions of the peptide with detergents. The prepared oligomeric solutions were analyzed with blue native and sodium dodecyl sulfate polyacrylamide gel electrophoresis, as well as with infrared (IR) spectroscopy. The IR spectra indicated a well-defined β-sheet structure of the prepared oligomers. We also found a relationship between the size/molecular weight of the Aβ42 oligomers and their IR spectra: The position of the main amide I′ band of the peptide backbone correlated with oligomer size, with larger oligomers being associated with lower wavenumbers. This relationship explained the time-dependent band shift observed in time-resolved IR studies of Aβ42 aggregation in the absence of detergents, during which the oligomer size increased. In addition, the bandwidth of the main IR band in the amide I′ region was found to become narrower with time in our time-resolved aggregation experiments, indicating a more homogeneous absorption of the β-sheets of the oligomers after several hours of aggregation. This is predominantly due to the consumption of smaller oligomers in the aggregation process.

Keywords
Amyloid-beta peptide, antiparallel beta-sheet, FTIR spectroscopy, infrared spectroscopy, oligomer
National Category
Biological Sciences
Identifiers
urn:nbn:se:su:diva-191785 (URN)10.1021/acschemneuro.0c00642 (DOI)000618157100010 ()33455165 (PubMedID)
Available from: 2021-04-27 Created: 2021-04-27 Last updated: 2023-08-28Bibliographically approved
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ORCID iD: ORCID iD iconorcid.org/0000-0001-5784-7673

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