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Nanostructure-based functions are omnipresent in nature and essential for the diversity of life. Unlike small molecules, which are often inhibitors of enzymes or biomimetics with established methods of elucidation, we show that functions of nanoscale structures in cells are complex and can implicate system-level effects such as the regulation of energy and redox homeostasis. Herein, we design a platinum(II)-containing tripeptide that assembles into intracellular fibrillar nanostructures upon molecular rearrangement in the presence of endogenous H

Nanostructure-based functions are omnipresent in nature and essential for the diversity of life. Unlike small molecules, which are often inhibitors of enzymes or biomimetics with established methods of elucidation, we show that functions of nanoscale structures in cells are complex and can implicate system-level effects such as the regulation of energy and redox homeostasis. Herein, we design a platinum (II) containing tripeptide that assembles into intracellular fibrillar nanostructures upon molecular rearrangement in the presence of endogenous H2O2. The formed nanostructures blocked metabolic functions, including aerobic glycolysis and oxidative phosphorylation, thereby shutting down ATP production. As a consequence, ATP-dependent actin formation and glucose metabolite- dependent histone deacetylase activity are downregulated. We demonstrate that assembly-driven nanomaterials offer a rich avenue to achieve broad-spectrum bioactivities that could provide new opportunities in drug discovery.

The COVID-19 pandemic has catalyzed the development of online learning formats in virtually all areas of medical education. In pediatric ethics, online learning may not only substitute but also offer specific advantages over traditional classroom teaching. Many pediatricians rate their ethics education as poor and medical ethics education lacks evaluation, especially regarding the students' needs. The aim of this project was to implement and evaluate a novel interactive distance learning approach to engage medical students in pediatric ethics education.An online ethics course was designed and delivered between May and June 2020. Core item of this course was a moderated, written forum discussion spanning several days. Evaluation was mixed methods. We evaluated the effectiveness of the course in terms of quality of the learning environment with a particular focus on relevance to students as well as interactive learning and reflective thinking. The Constructivist On-Line Learning Environment Survey (COLLES) was used to evaluate six different domains of the course. Data are presented as mean (standard deviation [SD]). The respective score range is 1-5, whereby a score of 4 or 5 means that the participants indicated the corresponding item as frequently or almost always present.Responses were available from 104 (78.3%) of the 133 participating students. "Relevance" yielded a score of 4.17 (0.83), "reflective thinking" a score of 4.22 (0.83). "Interactivity" was scored 3.76 (0.99) and "tutor support" 4.72 (0.53). "Peer support" and "interpretation" scored 3.87 (0.98) and 4.49 (0.60), respectively. In qualitative analysis, students particularly valued the structure of the course, the relevance for their professional practice, their active participation and the incentive to reflective thinking. Students also indicated that this was an innovative and exciting format, which fills a current educational gap and should hence be continued beyond the pandemic.In conclusion, students actively engaged in online learning and perceived this ethics course as highly relevant for their professional practice.Die COVID-19-Pandemie hat die Entwicklung von Online-Lernformaten in nahezu allen Bereichen der medizinischen Ausbildung beschleunigt. Im Bereich der pädiatrischen Ethik könnte Onlineunterricht den traditionellen Präsenzunterricht nicht nur ersetzen, sondern diesem gegenüber auch konkrete Vorteile bieten. Viele Pädiaterinnen und Pädiater bezeichnen ihre ethische Ausbildung als schlecht, und der medizinethischen Ausbildung fehlt es an Evaluation, insbesondere hinsichtlich der Bedürfnisse der Studierenden. Das Ziel dieses Projekts war es, einen neuen interaktiven Ansatz für Fernunterricht zu implementieren und evaluieren, mit dem Medizinstudierenden Ethik in der Pädiatrie vermittelt werden soll.Ein Online-Ethikkurs wurde entworfen und von Mai bis Juni 2020 abgehalten. Kernstück dieses Kurses war eine mehrtägige moderierte, schriftliche Forumsdiskussion. Bei der Evaluation wurde ein Methodenmix angewendet. Dabei wurden die Effektivität des Kurses hinsichtlich der Qualität der Lernumgebung unter besonderer Berücksichtigung der Relevanz für die Studierenden sowie des interaktiven Lernens und des reflexiven Denkens evaluiert. Mithilfe des Constructivist On-Line Learning Environment Survey (COLLES; konstruktivistische Bewertung der Online-Lernumgebung) wurden sechs unterschiedliche Aspekte des Kurses bewertet. Die Daten sind als Mittelwert (Standardabweichung [SD]) angegeben. Der jeweilige Wertebereich ist 1-5, wobei die Werte 4 oder 5 anzeigen, dass die Teilnehmenden das jeweilige Item als häufig oder fast immer vorhanden einstuften.Von 104 (78,3%) der insgesamt 133 Studierenden, die an dem Kurs teilnahmen, lagen Antworten vor. „Relevanz“ wurde mit einem Wert von 4,17 (0,83) bewertet, „reflexives Denken“ mit einem Wert von 4,22 (0,83). Der Wert von „Interaktivität“ betrug 3,76 (0,99) und von „Unterstützung durch die Dozentin/den Dozenten“ 4,72 (0,53). „Gegenseitige Unterstützung in der Gruppe“ und „Interpretation“ bewerteten die Teilnehmenden jeweils mit 3,87 (0,98) und 4,49 (0,60). Die qualitative Analyse zeigt, dass die Studierenden vor allem die Struktur des Kurses, die Relevanz für ihre Berufspraxis, ihre aktive Beteiligung sowie den Anreiz zum reflexiven Denken schätzten. Zudem gaben die Studierenden an, dass es sich um ein innovatives und spannendes Format handle, das eine derzeit bestehende Ausbildungslücke schließe und daher auch über die Pandemie hinaus fortgeführt werden solle.Abschließend ist festzuhalten, dass sich die Studierenden aktiv am Onlineunterricht beteiligten und sie diesen Ethikkurs als überaus relevant für ihre berufliche Praxis wahrnahmen.

Nanostructure-based functions are omnipresent in biology and essential for the diversity of life. Despite their importance, it is difficult to establish mechanisms that define their bioactivity and rationalize them through synthetic designs. As such, strategies that connect bioactive functions through structure formation are scarce. Herein, we design a near-infrared emitting platinum (II)-tripeptide that undergoes a rearrangement using endogenous H2O2 to rapidly assemble into fibrillar superstructures. The resultant assembly inhibits the metabolism of aggressive metastatic MDA-MB-231 cells and A549 cells at the systemic level by blocking aerobic glycolysis and oxidative phosphorylation, thereby shutting down ATP production. Hence, ATP-dependent actin formation and glucose metabolite-dependent histone deacetylase activity are downregulated, leading to apoptosis. By demonstrating that assembly-driven functions can inhibit broad biological pathways, supramolecular nanostructures could offer the next generation biomedical solutions beyond conventional applications.

Superamphiphobic surfaces are commonly associated with superior anticontamination and antifouling properties. Visually, this is justified by their ability to easily shed off drops and contaminants. However, on micropillar arrays, tiny droplets are known to remain on pillars' top faces while the drop advances. This raises the question of whether remnants remain even on nanostructured superamphiphobic surfaces. Are superamphiphobic surfaces really self-cleaning? Here we investigate the presence of microdroplet contaminants on three nanostructured superamphiphobic surfaces. After brief contact with liquids having different volatilities and surface tension (water, ethylene glycol, hexadecane, and an ionic liquid), confocal microscopy reveals a "blanket-like" layer of microdroplets remaining on the surface. It appears that the phenomenon is universal. Notably, when placing subsequent drops onto the contaminated surface, they are still able to roll off. However, adhesion forces can gradually increase by up to 3 times after repeated liquid drop contact. Therefore, we conclude that superamphiphobic surfaces do not warrant self-cleaning and anticontamination capabilities at sub-micrometric length scales.

One of the dreams of nanotechnology is to create tiny objects, nanobots, that are able to perform difficult tasks in dimensions and locations that are not directly accessible. One basic function of these nanobots is motility. Movements created by self-propelled micro- and nanovehicles are usually dependent on the production of propellants from catalytic reactions of fuels present in the environment. Developing self-powered nanovehicles with internally stored fuels that display motion regulated by external stimuli represents an intriguing and challenging alternative. Herein, a one-step preparation of fuel-containing nanovehicles that feature a motion that can be regulated by external stimuli is reported. Nanovehicles are prepared via a sol-gel process confined at the oil/water interface of miniemulsions. The nanovehicles display shapes ranging from mushroom-like to truncated cones and a core-shell structure so that the silica shell acts as a hull for the nanovehicles while the core is used to store the fuel. Azo-based initiators are loaded in the nanovehicles, which are activated to release nitrogen gas upon increase of temperature or exposure to UV light. Enhanced diffusion of nanovehicles is achieved upon decomposition of the fuel.

We monitor the self-cleaning process on a single-particle level and quantify the involved forces., Despite the enormous interest in superhydrophobicity for self-cleaning, a clear picture of contaminant removal is missing, in particular, on a single-particle level. Here, we monitor the removal of individual contaminant particles on the micrometer scale by confocal microscopy. We correlate this space- and time-resolved information with measurements of the friction force. The balance of capillary and adhesion force between the drop and the contamination on the substrate determines the friction force of drops during self-cleaning. These friction forces are in the range of micro-Newtons. We show that hydrophilic and hydrophobic particles hardly influence superhydrophobicity provided that the particle size exceeds the pore size or the thickness of the contamination falls below the height of the protrusions. These detailed insights into self-cleaning allow the rational design of superhydrophobic surfaces that resist contamination as demonstrated by outdoor environmental (>200 days) and industrial standardized contamination experiments.

The synthesis and physicochemical characterization of supramolecular polymers with tunable assembly profiles offer exciting opportunities, involving the development of new biomedical carriers. Because synthetic nanocarriers aim to transport substances across or toward cellular membranes, we evaluated the interactions of amphiphilic peptide-based supramolecular polymers with lipid bilayers. Here, we focused on nanorod-like supramolecular polymers, obtained from two C3-symmetric dendritic peptide amphiphiles with alternating Phe/His sequences, equipped with a peripheral tetraethylene glycol dendron (C3-PH) or charged ethylenediamine end groups (C3-PH+). Triggered by pH changes, these amphiphiles assemble reversibly. Our results show that the supramolecular polymers have an impact on the lipid order in model membranes. Changes in the lipid order were observed depending on the charge state of the amphiphilic building blocks, as well as the chemical composition and physical properties of the bilayer. Furthermore, we further performed cell viability assays with the C3-PH+ and C3-PH supramolecular polymers. For C3-PH, the cell viability and extent of proliferation were decreased and the membrane permeability was enhanced, indicating a strong interaction of the polymer with cellular membranes. The results have implications for the design of novel pH-switchable supramolecular drug carriers and delivery vehicles that can respond to an altered microenvironment of tumorous or inflamed tissue.

Biofilm formation is most commonly combatted with antibiotics or biocides. However, proven toxicity and increasing resistance of bacteria increase the need for alternative strategies to prevent adhesion of bacteria to surfaces. Chemical modification of the surfaces by tethering of functional polymer brushes or films provides a route toward antifouling coatings. Furthermore, nanorough or superhydrophobic surfaces can delay biofilm formation. Here we show that submicrometer-sized roughness can outweigh surface chemistry by testing the adhesion of E. coli to surfaces of different topography and wettability over long exposure times (>7 days). Gram-negative and positive bacterial strains are tested for comparison. We show that an irregular three-dimensional layer of silicone nanofilaments suppresses bacterial adhesion, both in the presence and absence of an air cushion. We hypothesize that a 3D topography can delay biofilm formation (i) if bacteria do not fit into the pores of the coating or (ii) if bending of the bacteria is required to adhere. Thus, such a 3D topography offers an underestimated possibility to design antibacterial surfaces that do not require biocides or antibiotics.

This work analyzes the intracellular fate of protein-based nanocarriers along their endolysosomal pathway by means of correlative light and electron microscopy methods. To unambiguously identify the nanocarriers and their degradation remnants in the cellular environment, they are labeled with fluorescent, inorganic nanoplatelets. This allows tracking the nanocarriers on their intracellular pathway by means of electron microscopy imaging. From the present data, it is possible to identify different cell compartments in which the nanocarriers are processed. Finally, three different terminal routes for the intracellular destiny of the nanocarriers are presented. These findings are important to reveal the degradation process of protein nanocapsules and contribute to the understanding of the therapeutic success of an encapsulated drug.