TY - JOUR A1 - Möckel, J. A1 - Brangsch, J. A1 - Reimann, C. A1 - Kaufmann, Jan Ole A1 - Sack, I. A1 - Mangarova, D. B. A1 - Kader, A. A1 - Taupitz, M. A1 - Adams, L. C. A1 - Keller, S. A1 - Ludwig, A. A1 - Hamm, B. A1 - Botnar, R. M. A1 - Makowski, M. R. T1 - Assessment of Albumin ECM Accumulation and Inflammation as Novel In Vivo Diagnostic Targets for Multi-Target MR Imaging JF - Biology N2 - Atherosclerosis is a progressive inflammatory vascular disease characterized by endothelial dysfunction and plaque burden. Extracellular matrix (ECM)-associated plasma proteins play an important role in disease development. Our magnetic resonance imaging (MRI) study investigates the feasibility of using two different molecular MRI probes for the simultaneous assessment of ECM-associated intraplaque albumin deposits caused by endothelial damage and progressive inflammation in atherosclerosis. Male apolipoprotein E-deficient (ApoE-/-)-mice were fed a high-fat diet (HFD) for 2 or 4 months. Another ApoE-/--group was treated with pravastatin and received a HFD for 4 months. T1- and T2*-weighted MRI was performed before and after albumin-specific MRI probe (gadofosveset) administration and a macrophage-specific contrast agent (ferumoxytol). Thereafter, laser ablation inductively coupled plasma mass spectrometry and histology were performed. With advancing atherosclerosis, albumin-based MRI signal enhancement and ferumoxytol-induced signal loss areas in T2*-weighted MRI increased. Significant correlations between contrast-to-noise-ratio (CNR) post-gadofosveset and albumin stain (R2 = 0.78, p < 0.05), and signal loss areas in T2*-weighted MRI with Perls’ Prussian blue stain (R2 = 0.83, p < 0.05) were observed. No interference of ferumoxytol with gadofosveset enhancement was detectable. Pravastatin led to decreased inflammation and intraplaque albumin. Multi-target MRI combining ferumoxytol and gadofosveset is a promising method to improve diagnosis and treatment monitoring in atherosclerosis. KW - Magnetic resonance imaging KW - MRI KW - Imaging KW - Human serum albumin KW - Extracellular matrix KW - Macrophages KW - Contrast agent KW - Atherosclerotic plaques KW - Gadofosveset KW - Aneurysm PY - 2021 UR - https://nbn-resolving.org/urn:nbn:de:kobv:b43-536725 DO - https://doi.org/10.3390/biology10100964 VL - 10 IS - 10 SP - 1 EP - 16 PB - MDPI CY - Basel AN - OPUS4-53672 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Schröder, K. A1 - Meyer-Plath, Asmus A1 - Keller, D. A1 - Ohl, A. T1 - On the Applicability of Plasma Assisted Chemical Micropatterning to Different Polymeric Biomaterials JF - Plasmas and polymers N2 - A plasma process sequence has been developed to prepare chemical micropatterns on polymeric biomaterial surfaces. These patterns induce a guided localized cell layover at microscopic dimension. Two subsequent plasma steps are applied. In the first functionalization step a microwave ammonia plasma introduces amino groups to obtain areas for very good cell adhesion; the second passivation step combines pattern generation and creation of cell repelling areas. This downstream microwave hydrogen plasma process removes functional groups and changes the linkages of polymer chains at the outermost surfaces. Similar results have been obtained on different polymers including polystyrene (PS), polyhydroxyethylmethacrylate (PHEMA), polyetheretherketone (PEEK), polyethyleneterephthalate (PET) and polyethylenenaphthalate (PEN). Such a rather universal chemical structuring process could widen the availability of biomaterials with specific surface preparations. KW - Microwave plasma KW - Ammonia KW - Hydrogen KW - Polymer surface KW - Cell culture KW - XPS KW - Fluorescence PY - 2002 DO - https://doi.org/10.1023/A:1016239302194 SN - 1084-0184 SN - 1572-8978 VL - 7 IS - 2 SP - 103 EP - 125 PB - Plenum Press CY - New York, NY AN - OPUS4-1729 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Keller, A. A1 - Kopyra, J. A1 - Gothelf, K.V. A1 - Bald, Ilko T1 - Electron-induced damage of biotin studied in the gas phase and in the condensed phase at a single-molecule level JF - New journal of physics N2 - Biotin is an essential vitamin that is, on the one hand, relevant for the metabolism, gene expression and in the cellular response to DNA damage and, on the other hand, finds numerous applications in biotechnology. The functionality of biotin is due to two particular sub-structures, the ring structure and the side chain with carboxyl group. The heterocyclic ring structure results in the capability of biotin to form strong intermolecular hydrogen and van der Waals bonds with proteins such as streptavidin, whereas the carboxyl group can be employed to covalently bind biotin to other complex molecules. Dissociative electron attachment (DEA) to biotin results in a decomposition of the ring structure and the carboxyl group, respectively, within resonant features in the energy range 0–12 eV, thereby preventing the capability of biotin for intermolecular binding and covalent coupling to other molecules. Specifically, the fragment anions (M–H)-, (M–O)-, C3N2O-, CH2O2-, OCN-, CN-, OH- and O- are observed, and exemplarily the DEA cross section of OCN- formation is determined to be 3 × 10-19 cm². To study the response of biotin to electrons within a complex condensed environment, we use the DNA origami technique and determine a dissociation yield of (1.1 ± 0.2) × 10-14 cm² at 18 eV electron energy, which represents the most relevant energy for biomolecular damage induced by secondary electrons. The present results thus have important implications for the use of biotin as a label in radiation experiments. KW - Low-energy electrons KW - DNA radiation damage KW - Biotin KW - Atomic force microscopy KW - Anions KW - Mass spectrometry PY - 2013 DO - https://doi.org/10.1088/1367-2630/15/8/083045 SN - 1367-2630 VL - 15 SP - 083045-1 - 083045-14 PB - IOP Publishing Ltd. AN - OPUS4-29610 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Prinz, J. A1 - Schreiber, B. A1 - Olejko, L. A1 - Oertel, J. A1 - Rackwitz, J. A1 - Keller, A. A1 - Bald, Ilko T1 - DNA origami substrates for highly sensitive surface-enhanced Raman scattering JF - The journal of physical chemistry letters N2 - DNA nanotechnology holds great promise for the fabrication of novel plasmonic nanostructures and the potential to carry out single-molecule measurements using optical spectroscopy. Here, we demonstrate for the first time that DNA origami nanostructures can be exploited as substrates for surface-enhanced Raman scattering (SERS). Gold nanoparticles (AuNPs) have been arranged into dimers to create intense Raman scattering hot spots in the interparticle gaps. AuNPs (15 nm) covered with TAMRA-modified DNA have been placed at a nominal distance of 25 nm to demonstrate the formation of Raman hot spots. To control the plasmonic coupling between the nanoparticles and thus the field enhancement in the hot spot, the size of AuNPs has been varied from 5 to 28 nm by electroless Au deposition. By the precise positioning of a specific number of TAMRA molecules in these hot spots, SERS with the highest sensitivity down to the few-molecule level is obtained. KW - DANN Origami KW - Surface-enhanced Raman scattering KW - Nanoparticles KW - TAMRA PY - 2013 DO - https://doi.org/10.1021/jz402076b SN - 1948-7185 VL - 4 IS - 23 SP - 4140 EP - 4145 PB - ACS CY - Washington, DC AN - OPUS4-29907 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Oertel, J. A1 - Keller, A. A1 - Prinz, J. A1 - Schreiber, B. A1 - Hübner, R. A1 - Kerbusch, J. A1 - Bald, Ilko A1 - Fahmy, K. T1 - Anisotropic metal growth on phospholipid nanodiscs via lipid bilayer expansion JF - Scientific Reports N2 - Self-assembling biomolecules provide attractive templates for the preparation of metallic nanostructures. However, the intuitive transfer of the “outer shape” of the assembled macromolecules to the final metallic particle depends on the intermolecular forces among the biomolecules which compete with interactions between template molecules and the metal during metallization. The shape of the bio-template may thus be more dynamic than generally assumed. Here, we have studied the metallization of phospholipid nanodiscs which are discoidal particles of ~10 nm diameter containing a lipid bilayer ~5 nm thick. Using negatively charged lipids, electrostatic adsorption of amine-coated Au nanoparticles was achieved and followed by electroless gold deposition. Whereas Au nanoparticle adsorption preserves the shape of the bio-template, metallization proceeds via invasion of Au into the hydrophobic core of the nanodisc. Thereby, the lipidic phase induces a lateral growth that increases the diameter but not the original thickness of the template. Infrared spectroscopy reveals lipid expansion and suggests the existence of internal gaps in the metallized nanodiscs, which is confirmed by surface-enhanced Raman scattering from the encapsulated lipids. Interference of metallic growth with non-covalent interactions can thus become itself a shape-determining factor in the metallization of particularly soft and structurally anisotropic biomaterials. KW - Lipid Nanodiscs KW - Metal nanoparticles KW - Infrared spectroscopy KW - Surface-enhanced Raman scattering PY - 2016 UR - https://nbn-resolving.org/urn:nbn:de:kobv:b43-364303 UR - http://www.nature.com/articles/srep26718 DO - https://doi.org/10.1038/srep26718 SN - 2045-2322 VL - 6 SP - 26718-1 EP - 26718-9 PB - Nature Publishing Group CY - London, UK AN - OPUS4-36430 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Kopyra, J. A1 - Keller, A. A1 - Bald, Ilko T1 - On the role of fluoro-substituted nucleosides in DNA radiosensitization for tumor radiation therapy JF - RSC Advances N2 - Gemcitabine (2',2'-difluorocytidine) is a well-known radiosensitizer routinely applied in concomitant chemoradiotherapy. During irradiation of biological media with high-energy radiation secondary low-energy (<10 eV) electrons are produced that can directly induce chemical bond breakage in DNA by dissociative electron attachment (DEA). Here, we investigate and compare DEA to the three molecules 2'-deoxycytidine, 2'-deoxy-5-fluorocytidine, and gemcitabine. Fluorination at specific molecular sites, i.e., nucleobase or sugar moiety, is found to control electron attachment and subsequent dissociation pathways. The presence of two fluorine atoms at the sugar ring results in more efficient electron attachment to the sugar moiety and subsequent bond cleavage. For the formation of the dehydrogenated nucleobase anion, we obtain an enhancement factor of 2.8 upon fluorination of the sugar, whereas the enhancement factor is 5.5 when the nucleobase is fluorinated. The observed fragmentation reactions suggest enhanced DNA strand breakage induced by secondary electrons when gemcitabine is incorporated into DNA. KW - Dissociative electron attachment KW - DNA radiation damage KW - Gemcitabine KW - DNA radiosensitizer KW - Tumor radiation therapy PY - 2014 UR - https://nbn-resolving.org/urn:nbn:de:kobv:b43-302872 DO - https://doi.org/10.1039/c3ra46735j SN - 2046-2069 VL - 4 IS - 13 SP - 6825 EP - 6829 PB - RSC Publishing CY - London AN - OPUS4-30287 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Bald, Ilko A1 - Keller, A. T1 - Molecular processes studied at a single-molecule level using DNA origami nanostructures and atomic force microscopy JF - Molecules N2 - DNA origami nanostructures allow for the arrangement of different functionalities such as proteins, specific DNA structures, nanoparticles, and various chemical modifications with unprecedented precision. The arranged functional entities can be visualized by atomic force microscopy (AFM) which enables the study of molecular processes at a single-molecular level. Examples comprise the investigation of chemical reactions, electron-induced bond breaking, enzymatic binding and cleavage events, and conformational transitions in DNA. In this paper, we provide an overview of the advances achieved in the field of single-molecule investigations by applying atomic force microscopy to functionalized DNA origami substrates. KW - DNA origami KW - atomic force microscopy KW - single-molecule analysis KW - DNA radiation damage KW - protein binding KW - enzyme reactions KW - G quadruplexes PY - 2014 UR - https://nbn-resolving.org/urn:nbn:de:kobv:b43-314343 DO - https://doi.org/10.3390/molecules190913803 SN - 1420-3049 VL - 19 IS - 9 SP - 13803 EP - 13823 PB - MDPI CY - Basel AN - OPUS4-31434 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Hakim, I. A1 - Schumacher, David A1 - Sundar, V. A1 - Donaldson, S. A1 - Creuz, A. A1 - Schneider, R. A1 - Keller, J. A1 - Browning, C. A1 - May, D. A1 - Abo Ras, M. A1 - Meyendorf, N. ED - Chimenti, D. E. ED - Bond, L. J. T1 - Volume imaging NDE and serial sectioning of carbon fiber composites T2 - AIP Conference Proceedings N2 - A composite material is a combination of two or more materials with very different mechanical, thermal and electrical properties. The various forms of composite materials, due to their high material properties, are widely used as structural materials in the aviation, space, marine, automobile, and sports industries. However, some defects like voids, delamination, or inhomogeneous fiber distribution that form during the fabricating processes of composites can seriously affect the mechanical properties of the composite material. In this study, several imaging NDE techniques such as: thermography, high frequency eddy current, ultrasonic, x-ray radiography, x-ray laminography, and high resolution x-ray CT were conducted to characterize the microstructure of carbon fiber composites. Then, a 3D analysis was implemented by the destructive technique of serial sectioning for the same sample tested by the NDE methods. To better analyze the results of this work and extract a clear volume image for all features and defects contained in the composite material, an intensive comparison was conducted among hundreds of 3D-NDE and multi serial sections’ scan images showing the microstructure variation. T2 - 44TH ANNUAL REVIEW OF PROGRESS IN QUANTITATIVE NONDESTRUCTIVE EVALUATION CY - Provo, Utah, USA DA - 16.07.2017 KW - Carbon fiber reinforced polymers KW - Non-destructive testing KW - Thermography KW - Eddy current KW - Ultrasound KW - X-ray radiography KW - X-ray laminography KW - X-ray computed tomography KW - Serial sectioning PY - 2018 DO - https://doi.org/10.1063/1.5031590 VL - 1949 SP - 120003-1 EP - 120003-10 PB - AIP Publishing AN - OPUS4-45173 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Keller, S. A1 - Borde, T. A1 - Brangsch, J. A1 - Reimann, C. A1 - Kader, A. A1 - Schulze, D. A1 - Buchholz, R. A1 - Kaufmann, Jan Ole A1 - Karst, U. A1 - Schellenberger, E. A1 - Hamm, B. A1 - Makowski, M. R. T1 - Assessment of the hepatic tumor extracellular matrix using elastin‑specific molecular magnetic resonance imaging in an experimental rabbit cancer model JF - Scientific Reports N2 - To investigate the imaging performance of an elastin-specific molecular magnetic resonance imaging (MRI) probe with respect to the extracellular matrix (ECM) in an experimental hepatic cancer model. Twelve rabbits with hepatic VX2 tumors were examined using 3 T MRI 14, 21, and 28 days after tumor implantation for two subsequent days (gadobutrol, day 1; elastin-specific probe, day 2). The relative enhancement (RE) of segmented tumor regions (central and margin) and the peritumoral matrix was calculated using pre-contrast and delayed-phase T1w sequences. MRI measurements were correlated to histopathology and element-specific and spatially resolved mass spectrometry (MS). Mixed-model analysis was performed to assess the performance of the elastin-specific probe. In comparison to gadobutrol, the elastin probe showed significantly stronger RE, which was pronounced in the tumor margin (day 14–28: P ≤ 0.007). In addition, the elastin probe was superior in discriminating between tumor regions (χ2(4) = 65.87; P < 0.001). MRI-based measurements of the elastin probe significantly correlated with the ex vivo elastinstain (R = .84; P <0 .001) and absolute gadolinium concentrations (ICP-MS: R = .73, P <0 .01). LA-ICP-MS imaging confirmed the colocalization of the elastin-specific probe with elastic fibers. Elastin-specific molecular MRI is superior to non-specific gadolinium-based contrast agents in imaging the ECM of hepatic tumors and the peritumoral tissue. KW - Elastin-specific molecular agent KW - Extracellular matrix KW - Hepatocellular carcinoma KW - Inductively coupled plasma mass spectroscopy KW - Laser ablation-inductively coupled plasma-mass spectrometry KW - Magnetic resonance imaging KW - MR imaging KW - ESMA KW - Gadolinium PY - 2020 UR - https://nbn-resolving.org/urn:nbn:de:kobv:b43-517360 DO - https://doi.org/10.1038/s41598-020-77624-8 VL - 10 IS - 1 SP - 20785 PB - Nature AN - OPUS4-51736 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Adams, L. C. A1 - Brangsch, J. A1 - Kaufmann, Jan Ole A1 - Mangarova, D. B. A1 - Moeckel, J. A1 - Kader, A. A1 - Buchholz, R. A1 - Karst, U. A1 - Botnar, R. M. A1 - Hamm, B. A1 - Makowski, M. R. A1 - Keller, S. T1 - Effect of Doxycycline on Survival in Abdominal Aortic Aneurysms in a Mouse Model JF - Contrast Media & Molecular Imaging N2 - Background. Currently, there is no reliable nonsurgical treatment for abdominal aortic aneurysm (AAA). This study, therefore, investigates if doxycycline reduces AAA growth and the number of rupture-related deaths in a murine ApoE−/− model of AAA and whether gadofosveset trisodium-based MRI differs between animals with and without doxycycline treatment. Methods. Nine ApoE−/− mice were implanted with osmotic minipumps continuously releasing angiotensin II and treated with doxycycline (30 mg/kg/d) in parallel. After four weeks, MRI was performed at 3T with a clinical dose of the albumin-binding probe gadofosveset (0.03 mmol/kg). Results were compared with previously published wild-type control animals and with previously studied ApoE−/− animals without doxycycline treatment. Differences in mortality were also investigated between these groups. Results. In a previous study, we found that approximately 25% of angiotensin II-infused ApoE−/− mice died, whereas in the present study, only one out of 9 angiotensin II-infused and doxycycline-treated ApoE−/− mice (11.1%) died within 4 weeks. Furthermore, doxycycline-treated ApoE−/− mice showed significantly lower contrast-to-noise (CNR) values in MRI compared to ApoE−/− mice without doxycycline treatment. In vivo measurements of relative signal enhancement (CNR) correlated significantly with ex vivo measurements of albumin staining (R2 = 0.58). In addition, a strong visual colocalization of albumin-positive areas in the fluorescence albumin staining with gadolinium distribution in LA-ICP-MS was shown. However, no significant difference in aneurysm size was observed after doxycycline treatment. Conclusion. The present experimental in vivo study suggests that doxycycline treatment may reduce rupture-related deaths in AAA by slowing endothelial damage without reversing aneurysm growth. KW - Ggadolinium KW - MRI KW - Magnetic resonance imaging KW - Osmotic minipumps KW - Tetracyclin KW - Antibiotics KW - Angiotensin II KW - LA-ICP-MS PY - 2021 UR - https://nbn-resolving.org/urn:nbn:de:kobv:b43-527015 DO - https://doi.org/10.1155/2021/9999847 SP - 9999847 PB - Hindawi CY - London AN - OPUS4-52701 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER -