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- ItemEMT-Induced Cell-Mechanical Changes Enhance Mitotic Rounding Strength(Weinheim : Wiley-VCH, 2020) Hosseini, Kamran; Taubenberger, Anna; Werner, Carsten; Fischer-Friedrich, ElisabethTo undergo mitosis successfully, most animal cells need to acquire a round shape to provide space for the mitotic spindle. This mitotic rounding relies on mechanical deformation of surrounding tissue and is driven by forces emanating from actomyosin contractility. Cancer cells are able to maintain successful mitosis in mechanically challenging environments such as the increasingly crowded environment of a growing tumor, thus, suggesting an enhanced ability of mitotic rounding in cancer. Here, it is shown that the epithelial–mesenchymal transition (EMT), a hallmark of cancer progression and metastasis, gives rise to cell-mechanical changes in breast epithelial cells. These changes are opposite in interphase and mitosis and correspond to an enhanced mitotic rounding strength. Furthermore, it is shown that cell-mechanical changes correlate with a strong EMT-induced change in the activity of Rho GTPases RhoA and Rac1. Accordingly, it is found that Rac1 inhibition rescues the EMT-induced cortex-mechanical phenotype. The findings hint at a new role of EMT in successful mitotic rounding and division in mechanically confined environments such as a growing tumor.
- ItemChemokine‐Capturing Wound Contact Layer Rescues Dermal Healing(Weinheim : Wiley-VCH, 2021) Schirmer, Lucas; Atallah, Passant; Freudenberg, Uwe; Werner, CarstenExcessive inflammation often impedes the healing of chronic wounds. Scavenging of chemokines by multiarmed poly(ethylene glycol)-glycosaminoglycan (starPEG-GAG) hydrogels has recently been shown to support regeneration in a diabetic mouse chronic skin wound model. Herein, a textile-starPEG-GAG composite wound contact layer (WCL) capable of selectively sequestering pro-inflammatory chemokines is reported. Systematic variation of the local and integral charge densities of the starPEG-GAG hydrogel component allows for tailoring its affinity profile for biomolecular signals of the wound milieu. The composite WCL is subsequently tested in a large animal (porcine) model of human wound healing disorders. Dampening excessive inflammatory signals without affecting the levels of pro-regenerative growth factors, the starPEG-GAG hydrogel-based WCL treatment induced healing with increased granulation tissue formation, angiogenesis, and deposition of connective tissue (collagen fibers). Thus, this biomaterials technology expands the scope of a new anti-inflammatory therapy toward clinical use.
- ItemIn situ identification and G4-PPI-His-Mal-dendrimer-induced reduction of early-stage amyloid aggregates in Alzheimer’s disease transgenic mice using synchrotron-based infrared imaging([London] : Macmillan Publishers Limited, part of Springer Nature, 2021) Benseny-Cases, Núria; Álvarez-Marimon, Elena; Aso, Ester; Carmona, Margarita; Klementieva, Oxana; Appelhans, Dietmar; Ferrer, Isidre; Cladera, JosepAmyloid plaques composed of Aβ amyloid peptides and neurofibrillary tangles are a pathological hallmark of Alzheimer Disease. In situ identification of early-stage amyloid aggregates in Alzheimer’s disease is relevant for their importance as potential targets for effective drugs. Synchrotron-based infrared imaging is here used to identify early-stage oligomeric/granular aggregated amyloid species in situ in the brain of APP/PS1 transgenic mice for the first time. Also, APP/PS1 mice show fibrillary aggregates at 6 and 12 months. A significant decreased burden of early-stage aggregates and fibrillary aggregates is obtained following treatment with poly(propylene imine) dendrimers with histidine-maltose shell (a neurodegenerative protector) in 6-month-old APP/PS1 mice, thus demonstrating their putative therapeutic properties of in AD models. Identification, localization, and characterization using infrared imaging of these non-fibrillary species in the cerebral cortex at early stages of AD progression in transgenic mice point to their relevance as putative pharmacological targets. No less important, early detection of these structures may be useful in the search for markers for non-invasive diagnostic techniques.
- ItemSerum lactate dehydrogenase activities as systems biomarkers for 48 types of human diseases([London] : Macmillan Publishers Limited, part of Springer Nature, 2021) Wu, Yuling; Lu, Caixia; Pan, Nana; Zhang, Meng; An, Yi; Xu, Mengyuan; Zhang, Lijuan; Guo, Yachong; Tan, LijuanMost human diseases are systems diseases, and systems biomarkers are better fitted for diagnostic, prognostic, and treatment monitoring purposes. To search for systems biomarker candidates, lactate dehydrogenase (LDH), a housekeeping protein expressed in all living cells, was investigated. To this end, we analyzed the serum LDH activities from 172,933 patients with 48 clinically defined diseases and 9528 healthy individuals. Based on the median values, we found that 46 out of 48 diseases, leading by acute myocardial infarction, had significantly increased (p < 0.001), whereas gout and cerebral ischemia had significantly decreased (p < 0.001) serum LDH activities compared to the healthy control. Remarkably, hepatic encephalopathy and lung fibrosis had the highest AUCs (0.89, 0.80), sensitivities (0.73, 0.56), and specificities (0.90, 0.91) among 48 human diseases. Statistical analysis revealed that over-downregulation of serum LDH activities was associated with blood-related cancers and diseases. LDH activities were potential systems biomarker candidates (AUCs > 0.8) for hepatic encephalopathy and lung fibrosis.
- ItemSpatial segregation of mixed-sized counterions in dendritic polyelectrolytes([London] : Macmillan Publishers Limited, part of Springer Nature, 2021) Kłos, J.S.; Paturej, J.Langevin dynamics simulations are utilized to study the structure of a dendritic polyelectrolyte embedded in two component mixtures comprised of conventional (small) and bulky counterions. We vary two parameters that trigger conformational properties of the dendrimer: the reduced Bjerrum length, λ∗B, which controls the strength of electrostatic interactions and the number fraction of the bulky counterions, fb, which impacts on their steric repulsion. We find that the interplay between the electrostatic and the counterion excluded volume interactions affects the swelling behavior of the molecule. As compared to its neutral counterpart, for weak electrostatic couplings the charged dendrimer exists in swollen conformations whose size remains unaffected by fb. For intermediate couplings, the absorption of counterions into the pervaded volume of the dendrimer starts to influence its conformation. Here, the swelling factor exhibits a maximum which can be shifted by increasing fb. For strong electrostatic couplings the dendrimer deswells correspondingly to fb. In this regime a spatial separation of the counterions into core–shell microstructures is observed. The core of the dendrimer cage is preferentially occupied by the conventional ions, whereas its periphery contains the bulky counterions.
- ItemUniversal size ratios of Gaussian polymers with complex architecture: radius of gyration vs hydrodynamic radius([London] : Macmillan Publishers Limited, part of Springer Nature, 2020) Haydukivska, Khristine; Blavatska, Viktoria; Paturej, JarosławWe study the impact of arm architecture of polymers with a single branch point on their structure in solvents. Many physical properties of polymer liquids strongly dependent on the size and shape measures of individual macromolecules, which in turn are determined by their topology. Here, we use combination of analytical theory, based on path integration method, and molecular dynamics simulations to study structural properties of complex Gaussian polymers containing fc linear branches and fr closed loops grafted to the central core. We determine size measures such as the gyration radius Rg and the hydrodynamic radii RH, and obtain the estimates for the size ratio Rg/RH with its dependence on the functionality f=fc+fr of grafted polymers. In particular, we obtain the quantitative estimate of the degree of compactification of these polymers with increasing number of closed loops fr as compared to linear or star-shape molecules of the same total molecular weight. Numerical simulations corroborate theoretical prediction that Rg/RH decreases towards unity with increasing f. These findings provide qualitative description of polymers with complex architecture in θ solvents.
- ItemPrecursor-surface interactions revealed during plasma-enhanced atomic layer deposition of metal oxide thin films by in-situ spectroscopic ellipsometry([London] : Macmillan Publishers Limited, part of Springer Nature, 2020) Kilic, Ufuk; Mock, Alyssa; Sekora, Derek; Gilbert, Simeon; Valloppilly, Shah; Melendez, Giselle; Ianno, Natale; Langell, Marjorie; Schubert, Eva; Schubert, MathiasWe find that a five-phase (substrate, mixed native oxide and roughness interface layer, metal oxide thin film layer, surface ligand layer, ambient) model with two-dynamic (metal oxide thin film layer thickness and surface ligand layer void fraction) parameters (dynamic dual box model) is sufficient to explain in-situ spectroscopic ellipsometry data measured within and across multiple cycles during plasma-enhanced atomic layer deposition of metal oxide thin films. We demonstrate our dynamic dual box model for analysis of in-situ spectroscopic ellipsometry data in the photon energy range of 0.7–3.4 eV measured with time resolution of few seconds over large numbers of cycles during the growth of titanium oxide (TiO2) and tungsten oxide (WO3) thin films, as examples. We observe cyclic surface roughening with fast kinetics and subsequent roughness reduction with slow kinetics, upon cyclic exposure to precursor materials, leading to oscillations of the metal thin film thickness with small but positive growth per cycle. We explain the cyclic surface roughening by precursor-surface interactions leading to defect creation, and subsequent surface restructuring. Atomic force microscopic images before and after growth, x-ray photoelectron spectroscopy, and x-ray diffraction investigations confirm structural and chemical properties of our thin films. Our proposed dynamic dual box model may be generally applicable to monitor and control metal oxide growth in atomic layer deposition, and we include data for SiO2 and Al2O3 as further examples.
- ItemEnhancing sub-bandgap external quantum efficiency by photomultiplication for narrowband organic near-infrared photodetectors([London] : Nature Publishing Group UK, 2021) Kublitski, Jonas; Fischer, Axel; Xing, Shen; Baisinger, Lukasz; Bittrich, Eva; Spoltore, Donato; Benduhn, Johannes; Vandewal, Koen; Leo, KarlDetection of electromagnetic signals for applications such as health, product quality monitoring or astronomy requires highly responsive and wavelength selective devices. Photomultiplication-type organic photodetectors have been shown to achieve high quantum efficiencies mainly in the visible range. Much less research has been focused on realizing near-infrared narrowband devices. Here, we demonstrate fully vacuum-processed narrow- and broadband photomultiplication-type organic photodetectors. Devices are based on enhanced hole injection leading to a maximum external quantum efficiency of almost 2000% at −10 V for the broadband device. The photomultiplicative effect is also observed in the charge-transfer state absorption region. By making use of an optical cavity device architecture, we enhance the charge-transfer response and demonstrate a wavelength tunable narrowband photomultiplication-type organic photodetector with external quantum efficiencies superior to those of pin-devices. The presented concept can further improve the performance of photodetectors based on the absorption of charge-transfer states, which were so far limited by the low external quantum efficiency provided by these devices.
- ItemVertical organic permeable dual-base transistors for logic circuits([London] : Nature Publishing Group UK, 2020) Guo, Erjuan; Wu, Zhongbin; Darbandy, Ghader; Xing, Shen; Wang, Shu-Jen; Tahn, Alexander; Göbel, Michael; Kloes, Alexander; Leo, Karl; Kleemann, HansThe main advantage of organic transistors with dual gates/bases is that the threshold voltages can be set as a function of the applied second gate/base bias, which is crucial for the application in logic gates and integrated circuits. However, incorporating a dual gate/base structure into an ultra-short channel vertical architecture represents a substantial challenge. Here, we realize a device concept of vertical organic permeable dual-base transistors, where the dual base electrodes can be used to tune the threshold voltages and change the on-currents. The detailed operation mechanisms are investigated by calibrated TCAD simulations. Finally, power-efficient logic circuits, e.g. inverter, NAND/AND computation functions are demonstrated with one single device operating at supply voltages of <2.0 V. We believe that this work offers a compact and technologically simple hardware platform with excellent application potential for vertical-channel organic transistors in complex logic circuits.
- ItemPseudo-chemotaxis of active Brownian particles competing for food(San Francisco, California, US : PLOS, 2020) Merlitz, Holger; Vuijk, Hidde D.; Wittmann, René; Sharma, Abhinav; Sommer, Jens-UweActive Brownian particles (ABPs) are physical models for motility in simple life forms and easily studied in simulations. An open question is to what extent an increase of activity by a gradient of fuel, or food in living systems, results in an evolutionary advantage of actively moving systems such as ABPs over non-motile systems, which rely on thermal diffusion only. It is an established fact that within confined systems in a stationary state, the activity of ABPs generates density profiles that are enhanced in regions of low activity, which is thus referred to as ‘anti-chemotaxis’. This would suggest that a rather complex sensoric subsystem and information processing is a precondition to recognize and navigate towards a food source. We demonstrate in this work that in non-stationary setups, for instance as a result of short bursts of fuel/food, ABPs do in fact exhibit chemotactic behavior. In direct competition with inactive, but otherwise identical Brownian particles (BPs), the ABPs are shown to fetch a larger amount of food. We discuss this result based on simple physical arguments. From the biological perspective, the ability of primitive entities to move in direct response to the available amount of external energy would, even in absence of any sensoric devices, encompass an evolutionary advantage.