Publikationen am Institut für Chemie und Biotechnik

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Bui, Van-Chien; Nguyen, Thi-Huong
Mechanics of leukemic T-cell. - In: Journal of molecular recognition, ISSN 1099-1352, Bd. 36 (2023), 7, e3019, S. 1-7

Cell mechanics is a factor that determines cell growth, migration, proliferation, or differentiation, as well as trafficking inside the cytoplasm and organization of organelles. Knowledge about cell mechanics is critical to gaining insight into these biological processes. Here, we used atomic force microscopy to examine the elasticity, an important parameter of cell mechanics, of non-adherent Jurkat leukemic T-cells in both interphase and mitotic phases. We found that the elasticity of an individual cell does not significantly change at interphase. When a cell starts to divide, its elasticity increases in the transition from metaphase to telophase during normal division while the cell is stiffened right after it enters mitosis during abnormal division. At the end of the division, the cell elasticity gradually returned to the value of the mother cell. These changes may originate from the changes in cell surface tension during modulating actomyosin at the cleavage furrow, redistributing cell organelles, and constricting the contractile ring to sever mother cell to form daughters. The difference in elasticity patterns suggests that there is a discrepancy in the redistribution of the cell organelles during normal and abnormal division.



https://doi.org/10.1002/jmr.3019
Nguyen, Thi-Huong; Wang, Hanqing; Chen, Li-Yu; Echtermeyer, Danny; Pliquett, Uwe
Modulating SARS-CoV-2 spike protein reactivity through moderate electric fields: a pathway to innovative therapies. - In: ACS omega, ISSN 2470-1343, Bd. 8 (2023), 48, S. 45952-45960

In the quest for effective COVID-19 treatments and vaccines, traditional biochemical methods have been paramount, yet the challenge of accommodating diverse viral mutants persists. Recent simulations propose an innovative physical strategy involving an external electric field applied to the SARS-CoV-2 spike protein, demonstrating a reduced viral binding potential. However, limited empirical knowledge exists regarding the characteristics of the spike protein after E-field treatment. Our study addresses this gap by employing diverse analytical techniques to elucidate the impact of low/moderate E-field intensity on the binding of the SARS-CoV-2 spike protein to the ACE2 receptor. Through comprehensive analysis, we unveil a substantial reduction in the spike protein binding capacity validated via enzyme-linked immunosorbent assay and quartz crystal microbalance experiments. Remarkably, the E-field exposure induces significant protein structure rearrangement, leading to an enhanced negative surface zeta potential confirmed by dynamic light scattering. Circular dichroism spectroscopy corroborates these structural changes, showing alterations in the secondary protein structures. This study provides insights into SARS-CoV-2 spike protein modification under an E-field pulse, potentially paving the way for nonbiochemical strategies to mitigate viral reactivity and opening avenues for innovative therapeutic and preventive approaches against COVID-19 and its evolving variants.



https://doi.org/10.1021/acsomega.3c06811
Hack, Jasmin; Jordan, Moritz; Schmitt, Alina; Raru, Melissa; Zorn, Hannes Sönke; Seyfarth, Alex; Eulenberger, Isabel; Geitner, Robert
Ilm-NMR-P31: an open-access 31P nuclear magnetic resonance database and data-driven prediction of 31P NMR shifts. - In: Journal of cheminformatics, ISSN 1758-2946, Bd. 15 (2023), 122, S. 1-12

This publication introduces a novel open-access 31P Nuclear Magnetic Resonance (NMR) shift database. With 14,250 entries encompassing 13,730 distinct molecules from 3,648 references, this database offers a comprehensive repository of organic and inorganic compounds. Emphasizing single-phosphorus atom compounds, the database facilitates data mining and machine learning endeavors, particularly in signal prediction and Computer-Assisted Structure Elucidation (CASE) systems. Additionally, the article compares different models for 31P NMR shift prediction, showcasing the database’s potential utility. Hierarchically Ordered Spherical Environment (HOSE) code-based models and Graph Neural Networks (GNNs) perform exceptionally well with a mean squared error of 11.9 and 11.4 ppm respectively, achieving accuracy comparable to quantum chemical calculations.



https://doi.org/10.1186/s13321-023-00792-y
Radivoievych, Aleksandar; Prylutska, Svitlana; Zolk, Oliver; Ritter, Uwe; Frohme, Marcus; Grebinyk, Anna
Comparison of sonodynamic treatment set-ups for cancer cells with organic sonosensitizers and nanosonosensitizers. - In: Pharmaceutics, ISSN 1999-4923, Bd. 15 (2023), 11, 2616, S. 1-21

Cancer sonodynamic therapy (SDT) is the therapeutic strategy of a high-frequency ultrasound (US) combined with a special sonosensitizer that becomes cytotoxic upon US exposure. The growing number of newly discovered sonosensitizers and custom US in vitro treatment solutions push the SDT field into a need for systemic studies and reproducible in vitro experimental set-ups. In the current research, we aimed to compare two of the most used and suitable SDT in vitro set-ups - “sealed well” and “transducer in well” - in one systematic study. We assessed US pressure, intensity, and temperature distribution in wells under US irradiation. Treatment efficacy was evaluated for both set-ups towards cancer cell lines of different origins, treated with two promising sonosensitizer candidates - carbon nanoparticle C60 fullerene (C60) and herbal alkaloid berberine. C60 was found to exhibit higher sonotoxicity toward cancer cells than berberine. The higher efficacy of sonodynamic treatment with a “transducer in well” set-up than a “sealed well” set-up underlined its promising application for SDT in vitro studies. The “transducer in well” set-up is recommended for in vitro US treatment investigations based on its US-field homogeneity and pronounced cellular effects. Moreover, SDT with C60 and berberine could be exploited as a promising combinative approach for cancer treatment.



https://doi.org/10.3390/pharmaceutics15112616
Huang, Tianbai; Kupfer, Stephan; Geitner, Robert; Gräfe, Stefanie
Computational modelling and mechanistic insight into light-driven CO dissociation of square-planar rhodium(I) complexes. - In: ChemPhotoChem, ISSN 2367-0932, Bd. n/a (2023), n/a, e202300219, S. 1-28

The activation step of Vaska-type Rh(I) complexes, such as the photocleavage of the Rh‑CO bond, plays an important role in the subsequent C-H activation. To elucidate the details of the photochemistry of Vaska-type Rh(I) complexes, such as trans-Rh(PMe3)2(CO)(Cl), we here present a computationally derived picture as obtained at the density functional level of theory (DFT) in combination with multireference wavefunction-based methods. We have identified that the photocleavage of CO proceeds via the metal-centered excited state, which is populated through intersystem crossing (ISC) from the dipole-allowed excited state S1. Moreover, the present study unraveled the reasons for the low C-H activation efficiency when using Rh featuring the bidentate ligand 1,2-bis(dimethylphosphino)ethane (dmpe), namely due to its unfavorable photochemical properties, i.e., the small driving force for light-induced CO loss and the fast deactivation of 3MC state back to the singlet ground state. In this study, we provide theoretical insight into mechanistic details underlying the light-induced CO dissociation process, for Rh complexes featuring PMe3 and dmpe ligands.



https://doi.org/10.1002/cptc.202300219
Soter, Marcus; Apte, Gurunath; Madkatte, Dikshita; Nguyen, Thi-Huong
Insights into the writing process of the mask-free nanoprinting fluid force microscopy technology. - In: Engineering for a changing world, (2023), 1.2.118, S. 1-13

Platelets are activated immediately when contacting with non-physiological surfaces. Minimization of surface-induced platelet activation is important not only for platelet storage but also for other blood-contacting devices and implants. Chemical surface modification tunes the response of cells to contacting surfaces, but it requires a long process involving many regulatory challenges to transfer into a marketable product. Biophysical modification overcomes these limitations by modifying only the surface topography of already approved materials. The available large and random structures on platelet storage bags do not cause a significant impact on platelets because of their smallest size (only 1-3 μm) compared to other cells. We have recently demonstrated the feasibility of the mask-free nanoprint fluid force microscope (FluidFM) technology for writing dot-grid and hexanol structures. Here, we demonstrated that the technique allows the fabrication of nanostructures of varying features. Characteristics of nanostructures including height, width, and cross-line were analyzed and compared using atomic force microscopy imaging. Based on the results, we identified several technical issues, such as the printing direction and shape of structures that directly altered nanofeatures during printing. We confirmed that FluidFM is a powerful technique to precisely fabricate a variety of desired nanostructures for the development of platelet/blood-contacting devices if technical issues during printing are well controlled.



https://doi.org/10.22032/dbt.58725
Motuziuk, Olexandr; Nozdrenko, Dmytro; Prylutska, Svitlana; Bogutska, Kateryna; Mishchenko, Iryna; Abramchuk, Olga; Khrapatyi, Sergii; Ritter, Uwe; Prylutskyy, Yuriy
C60 fullerene reduces the level of fluctuations in the force response of muscle gastrocnemius in chronically alcoholized rats. - In: Applied nanoscience, ISSN 2190-5517, Bd. 13 (2023), 10, S. 7057-7067

The biomechanical parameters of muscle gastrocnemius contraction and biochemical parameters of blood and muscle tissue in rats after chronic alcoholization for 3, 6, and 9 months were studied. The oral administration of C60 fullerene aqueous solution (C60FAS) at doses of 0.5, 1, and 2 mg/kg throughout the experiment was used as a therapeutic agent. C60FAS in each of the experimental groups was administered in three ways: 1 h before alcohol intake, together with alcohol, and 1 h after alcohol intake. The most significant positive effects were recorded when alcohol and C60FAS were administered together at the optimal dose of 1 mg/kg. So, the increase in muscle gastrocnemius contraction force was 20 ± 1%, 33 ± 2% and 65 ± 3% (p < 0.05) compared with control at 3, 6, and 9 months alcoholization, respectively, as well as a high level of its fluctuations correction was observed throughout the experiment. Biochemical parameters such as blood levels of creatinine, creatine phosphokinase, lactate and lactate dehydrogenase as well as pro- and antioxidant balance (content of hydrogen peroxide and reduced glutathione, as well as catalase, selenium-dependent glutathione peroxidase and superoxide dismutase activities) in muscle gastrocnemius tissues decreased from 15 ± 2% (3 months of alcoholization) to 45 ± 2% (9 months of alcoholization) (p < 0.05) compared to controls. The results indicate promising prospects for the use of water-soluble C60 fullerenes, as powerful antioxidants, for the correction of pathological conditions of the muscular system arising from alcohol intoxication.



https://doi.org/10.1007/s13204-023-02874-7
Motuziuk, Olexandr; Nozdrenko, Dmytro; Prylutska, Svitlana; Vareniuk, Igor; Bogutska, Kateryna; Braniuk, Serhii; Korotkyi, Olexandr; Prylutskyy, Yuriy; Ritter, Uwe; Piosik, Jacek
The effect of C60 fullerene on the mechanokinetics of muscle gastrocnemius contraction in chronically alcoholized rats. - In: Heliyon, ISSN 2405-8440, Bd. 9 (2023), 8, e18745, S. 1-10

The C60 fullerene effect (oral administration at a dose of 1 mg kg−1) on the selected biomechanical parameters of muscle gastrocnemius contraction, biochemical indicators of blood and muscle tissue as well as histological changes in rat muscle tissue after chronic alcoholization for 3, 6 and 9 months was studied in detail. Water-soluble C60 fullerenes were shown to reduce the pathological processes development in the muscle apparatus by an average of (35-40)%. In particular, they reduced the time occurrence of fatigue processes in muscle during the long-term development of alcoholic myopathy and inhibited oxidative processes in muscle, thereby preventing its degradation. These findings open up the possibility of using C60 fullerenes as potent antioxidants for the correction of the pathological conditions of the muscle system arising from alcohol intoxication.



https://doi.org/10.1016/j.heliyon.2023.e18745
Zavodovskiy, Danylo O.; Bulgakova, Nataliya V.; Sokolowska, Inna; Prylutskyy, Yuriy I.; Ritter, Uwe; Gonchar, Olga O.; Kostyukov, Alexander I.; Vlasenko, Oleh V.; Butowska, Kamila; Borowik, Agnieszka; Piosik, Jacek; Maznychenko, Andriy
Water-soluble pristine C60 fullerenes attenuate isometric muscle force reduction in a rat acute inflammatory pain model. - In: BMC musculoskeletal disorders, ISSN 1471-2474, Bd. 24 (2023), 606, S. 1-8

Background: Being a scavenger of free radicals, C60 fullerenes can influence on the physiological processes in skeletal muscles, however, the effect of such carbon nanoparticles on muscle contractility under acute muscle inflammation remains unclear. Thus, the aim of the study was to reveal the effect of the C60 fullerene aqueous solution (C60FAS) on the muscle contractile properties under acute inflammatory pain. Methods: To induce inflammation a 2.5% formalin solution was injected into the rat triceps surae (TS) muscle. High-frequency electrical stimulation has been used to induce tetanic muscle contraction. A linear motor under servo-control with embedded semi-conductor strain gauge resistors was used to measure the muscle tension. Results: In response to formalin administration, the strength of TS muscle contractions in untreated animals was recorded at 23% of control values, whereas the muscle tension in the C60FAS-treated rats reached 48%. Thus, the treated muscle could generate 2-fold more muscle strength than the muscle in untreated rats. Conclusions: The attenuation of muscle contraction force reduction caused by preliminary injection of C60FAS is presumably associated with a decrease in the concentration of free radicals in the inflamed muscle tissue, which leads to a decrease in the intensity of nociceptive information transmission from the inflamed muscle to the CNS and thereby promotes the improvement of the functional state of the skeletal muscle.



https://doi.org/10.1186/s12891-023-06719-w
Zeußel, Lisa; Schober, Andreas; Ullmann, Fabian; Krischok, Stefan; Heinrich, Doris; Singh, Sukhdeep
Visible-light-assisted donor-acceptor-Stenhouse-adduct-based reversible photoswitching on a laser-structurable OrmoComp substrate. - In: ACS applied polymer materials, ISSN 2637-6105, Bd. 5 (2023), 10, S. 8631-8640

Laser-assisted nanolithography of commercially available photoresists is offering a limitless designing opportunity in the micro- and nanostructuring of 3D organotypic cell culture scaffolds. Among them, chemically functionalized OrmoComp has shown promising improvement in cell adhesion that paves the way to assemble cellular entities on a desirable geometry. Establishing a photoswitchable chemistry on the OrmoComp surface may offer an additional degree of freedom to manipulate the surface chemistry locally and selectively. We have established the methods for functionalization of the photopolymerized OrmoComp surface with visible-light-switchable donor-acceptor Stenhouse adducts. Unlike other polymers, a photopolymerized OrmoComp surface appears to be optimal for reversible photothermal switching, offering the possibility to influence surface properties like absorption and hydrophilicity tremendously. Light-assisted chemical modulation between colored triene-2-ol and colorless cyclopentenone can be achieved to a size region as narrow as 20 μm. Thermal reversion to the original triene-2-ol state can be analyzed spectroscopically and observed with the naked eye.



https://doi.org/10.1021/acsapm.3c01766