Block Copolymer Giant Unilamellar Vesicles for High-Throughput Screening

Bottom-up synthetic cells offer the potential to study cellular processes with reduced complexity. Giant unilamellar vesicles (GUVs) can mimic cells in their morphological characteristics because their architecture is precisely controllable. We propose a block copolymer-based GUV system that can be used for high-throughput screening. Through droplet microfluidic methods, we produce double emulsions that then serve as templates for GUVs with adjustable inner, polymer membrane, and outer composition. Using flow cytometry, we are able to analyze tens of thousands of GUVs in a short amount of time, enabling their use for screening assays

Current Perspectives on Synthetic Compartments for Biomedical Applications

Nano- and micrometer-sized compartments composed of synthetic polymers are designed to mimic spatial and temporal divisions found in nature. Self-assembly of polymers into compartments such as polymersomes, giant unilamellar vesicles (GUVs), layer-by-layer (LbL) capsules, capsosomes, or polyion complex vesicles (PICsomes) allows for the separation of defined environments from the exterior. These compartments can be further engineered through the incorporation of (bio)molecules within the lumen or into the membrane, while the membrane can be decorated with functional moieties to produce catalytic compartments with defined structures and functions. Nanometer-sized compartments are used for imaging, theranostic, and therapeutic applications as a more mechanically stable alternative to liposomes, and through the encapsulation of catalytic molecules, i.e., enzymes, catalytic compartments can localize and act in vivo. On the micrometer scale, such biohybrid systems are used to encapsulate model proteins and form multicompartmentalized structures through the combination of multiple compartments, reaching closer to the creation of artificial organelles and cells. Significant progress in therapeutic applications and modeling strategies has been achieved through both the creation of polymers with tailored properties and functionalizations and novel techniques for their assembly

Structural and thermal evolution of the eastern Aar Massif: insights from structural field work and Raman thermometry

The thermo-kinematic evolution of the eastern Aar Massif, Swiss Alps, was investigated using peak temperature data estimated from Raman spectroscopy of carbonaceous material and detailed field analyses. New and compiled temperature-time constraints along the deformed and exhumed basement-cover contact allow us to (i) establish the timing of metamorphism and deformation, (ii) track long-term horizontal and vertical orogenic movements and (iii) assess the influence of temperature and structural inheritance on the kinematic evolution. We present a new shear zone map, structural cross sections and a step-wise retrodeformation. From ca.\;26\,Ma onwards, basement-involved deformation started with the formation of relatively discrete NNW-directed thrusts. Peak metamorphic isograds are weakly deformed by these thrusts, suggesting that they initiated before or during the metamorphic peak under ongoing burial in the footwall to the basal Helvetic roof thrust. Subsequent peak- to post-metamorphic deformation was dominated by steep, mostly NNW-vergent reverse faults (ca. 22–14 Ma). Field investigations demonstrate that these shear zones were steeper than 50∘ already at inception. This produced the massif-internal structural relief and was associated with large vertical displacements (7 km shortening vs. up to 11 km exhumation). From 14 Ma onwards, the eastern Aar massif exhumed “en bloc” (i.e., without significant differential massif-internal exhumation) in the hanging wall of frontal thrusts, which is consistent with the transition to strike-slip dominated deformation observed within the massif. Our results indicate 13 km shortening and 9 km exhumation between 14 Ma and present. Inherited normal faults were not significantly reactivated. Instead, new thrusts/reverse faults developed in the basement below syn-rift basins, and can be traced into overturned fold limbs in the overlying sediment, producing tight synclines and broad anticlines along the basement-cover contact. The sediments were not detached from their crystalline substratum and formed disharmonic folds. Our results highlight decreasing rheological contrasts between (i) relatively strong basement and (ii) relatively weak cover units and inherited faults at higher temperature conditions. Both the timing of basement-involved deformation and the structural style (shear zone dip) appear to be controlled by evolving temperature conditions

120 years of georesources research in Switzerland: the Swiss Geotechnical Commission (1899-2018)

Geological surveys have a wide range of tasks for their countries: to map the geology and to assess the georesources potential for metallic ores, industrial minerals, geothermal energy, fossil fuels, aggregates and groundwater. In Europe, most countries founded geological surveys around the mid-nineteenth century in order to create an overview of the geological resources they wanted to exploit. In Switzerland, at that time, the industrial revolution triggered a tremendous demand for infrastructure and energy raw materials. However, no national georesources institution was established when the nation-forming process among the 25 cantons culminated in the foundation of the Swiss Federal State in 1848. The Swiss Geological Survey was founded 138 years later in 1986. How did Switzerland map the country, assess the resource potential and provide fundamental data for land use planning without such an organisation? This paper elaborates on the evolution of Swiss institutions mandated to study the geological resources, with a focus on the Swiss Geotechnical Commission (SGTK, 1899-2018). Given the low financial resources, no long-term nation-wide investigation programs could be implemented. The commission's study program was mainly driven by external societal and political factors. World War I for example reactivated the search for coal which was intensively exploited during those years. Before and during World War II, the focus temporarily shifted to oil and gas exploration. From 1970 onwards, SGTK was involved in several applied research projects and collaborations with various industry partners. In this paper, we revisit the key turning points in the evolution of the commission's investigation program, including related financial and organisational aspects, and discuss how Switzerland's federalistic structure influenced the geological survey activities. The history of the SGTK represents an exemplification of how a nation managed its geological survey activities, until 1986 in the absence of a geological survey and without large hydrocarbon and metallic ore resources and a corresponding, significant mining industry. The SGTK case also shows that flexible, project-based investigations can be advantageous as they respond to current challenges at short notice. This could to some degree substitute the initial absence of a geological survey, as shown by the numerous SGTK monographs that are key references also 100 years after their publication.ISSN:1661-8734ISSN:1661-872

Structural and thermal evolution of the eastern Aar Massif: insights from structural field work and Raman thermometry

The thermo-kinematic evolution of the eastern Aar Massif, Swiss Alps, was investigated using peak temperature data estimated from Raman spectroscopy of carbonaceous material and detailed field analyses. New and compiled temperature-time constraints along the deformed and exhumed basement-cover contact allow us to (i) establish the timing of metamorphism and deformation, (ii) track long-term horizontal and vertical orogenic movements and (iii) assess the influence of temperature and structural inheritance on the kinematic evolution. We present a new shear zone map, structural cross sections and a step-wise retrodeformation. From ca.\;26\,Ma onwards, basement-involved deformation started with the formation of relatively discrete NNW-directed thrusts. Peak metamorphic isograds are weakly deformed by these thrusts, suggesting that they initiated before or during the metamorphic peak under ongoing burial in the footwall to the basal Helvetic roof thrust. Subsequent peak- to post-metamorphic deformation was dominated by steep, mostly NNW-vergent reverse faults (ca. 22–14 Ma). Field investigations demonstrate that these shear zones were steeper than 50∘ already at inception. This produced the massif-internal structural relief and was associated with large vertical displacements (7 km shortening vs. up to 11 km exhumation). From 14 Ma onwards, the eastern Aar massif exhumed “en bloc” (i.e., without significant differential massif-internal exhumation) in the hanging wall of frontal thrusts, which is consistent with the transition to strike-slip dominated deformation observed within the massif. Our results indicate 13 km shortening and 9 km exhumation between 14 Ma and present. Inherited normal faults were not significantly reactivated. Instead, new thrusts/reverse faults developed in the basement below syn-rift basins, and can be traced into overturned fold limbs in the overlying sediment, producing tight synclines and broad anticlines along the basement-cover contact. The sediments were not detached from their crystalline substratum and formed disharmonic folds. Our results highlight decreasing rheological contrasts between (i) relatively strong basement and (ii) relatively weak cover units and inherited faults at higher temperature conditions. Both the timing of basement-involved deformation and the structural style (shear zone dip) appear to be controlled by evolving temperature conditions.ISSN:1661-8734ISSN:1661-872

Synthetic Cells Revisited: Artificial Cells Construction Using Polymeric Building Blocks

Abstract The exponential growth of research on artificial cells and organelles underscores their potential as tools to advance the understanding of fundamental biological processes. The bottom–up construction from a variety of building blocks at the micro‐ and nanoscale, in combination with biomolecules is key to developing artificial cells. In this review, artificial cells are focused upon based on compartments where polymers are the main constituent of the assembly. Polymers are of particular interest due to their incredible chemical variety and the advantage of tuning the properties and functionality of their assemblies. First, the architectures of micro‐ and nanoscale polymer assemblies are introduced and then their usage as building blocks is elaborated upon. Different membrane‐bound and membrane‐less compartments and supramolecular structures and how they combine into advanced synthetic cells are presented. Then, the functional aspects are explored, addressing how artificial organelles in giant compartments mimic cellular processes. Finally, how artificial cells communicate with their surrounding and each other such as to adapt to an ever‐changing environment and achieve collective behavior as a steppingstone toward artificial tissues, is taken a look at. Engineering artificial cells with highly controllable and programmable features open new avenues for the development of sophisticated multifunctional systems

Automated extraction of orientation and stratigraphic thickness from geological maps

Geological maps are available for almost every region of the world and, therefore, represent the most commonly used source of information for earth scientists. Advances in computing power and the availability of digital elevation data have opened new possibilities to automatically extract quantitative information from geological maps, especially in regions with topographic relief and good bedrock exposure. We present an innovative approach to automatically extract orientation (dip direction/dip) and stratigraphic thickness from a 1:25′000 geological map vector data set of the Swiss Alps. The approach allows a rapid spatial overview on the orientation and thickness of a given geological unit over large areas. Key improvements of the approach with respect to commonly used 3D modelling approaches are its objectivity, rapidity and the possibility to classify and/or filter orientation and thickness model output after five numeric reliability parameters. The approach is designed to support authorities and the industry in performing a rapid screening of a given region and to early identify promising areas for potential mineral extraction projects. Large-scale spatial overviews on the orientation and thickness of geological units are of large interest in many other disciplines such as tectonic and stratigraphic reconstruction, hydrogeological or geotechnical analyses. Therefore, the approach will be widely applicable also beyond the evaluation of potential mineral resources.ISSN:0191-814

Orogen-Parallel Migration of Exhumation in the Eastern Aar Massif Revealed by Low-T Thermochronometry

New and published (U-Th)/He data on zircon, apatite, and zircon fission track ages constrain the thermal overprint and cooling history of the eastern Aar Massif, Switzerland. The timing and pattern of cooling is in agreement with independent kinematic and age constraints from exposed shear zones. This suggests that the cooling ages mainly reflect exhumation and that long-term exhumation-dynamics were mainly controlled by crustal-scale tectonic processes. Results of a statistical inverse model reveal significant diachrony in the timing of exhumation in the along-strike direction. Maximum exhumation rates ((Formula presented.) 1 mm/yr) were initially located in the central Aar Massif (from (Formula presented.) 22 to 10 Ma), then gradually migrated to the east between (Formula presented.) 10 Ma and present, while the central Aar Massif continued to exhume at slower rates ((Formula presented.) 0.5 mm/yr). The diachrony in the timing of exhumation may be explained by lateral variations in the inherited thickness or the density of the accreted European crust. We attribute the increase in exhumation rates between 2 Ma and present to enhanced glacial erosion. Nevertheless, the post 2 Ma exhumation pattern reflects a continuation of noncylindrical massif “growth” in the eastward orogen-parallel direction. This indicates that—although at slow rates—thick-skinned and buoyancy-driven compressional deformation, likely enhanced by the presence of easily erodible flysch units at the surface, might still be ongoing especially in the eastern Aar Massif. Noncylindrical massif-growth is likely to also affect other External Crystalline Massifs or orogens, but may be overlooked because studies often focus on single orogen-perpendicular transects.ISSN:2169-9313ISSN:0148-0227ISSN:2169-935

Enhanced Antimicrobial Activity and Structural Transitions of a Nanofibrillated Cellulose–Nisin Biocomposite Suspension

Resistance to antibiotics has posed a high demand for novel strategies to fight bacterial infections. Antimicrobial peptides (AMPs) are a promising alternative to conventional antibiotics. However, their poor solubility in water and sensitivity to degradation has limited their application. Here, we report the design of a smart, pH-responsive antimicrobial nanobiocomposite material based on the AMP nisin and 2,2,6,6-tetramethyl-1-piperidinyloxyl-oxidized nanofibrillated cellulose (TONFC). Morphological transformations of the nanoscale structure of nisin functionalized-TONFC fibrils were discovered at pH values between 5.8 and 8.0 using small-angle X-ray scattering. Complementary ζ potential measurements indicate that electrostatic attractions between the negatively charged TONFC surface and the positively charged nisin molecules are responsible for the integration of nisin. Modification of the pH level or increasing the ionic strength reduces the nisin binding capacity of TONFC. Biological evaluation studies using a bioluminescence-based reporter strain of Bacillus subtilis and a clinically relevant strain of Staphylococcus aureus indicated a significantly higher antimicrobial activity of the TONFC–nisin biocomposite compared to the pure nisin against both strains under physiological pH and ionic strength conditions. The in-depth characterization of this new class of antimicrobial biocomposite material based on nanocellulose and nisin may guide the rational design of sustainable antimicrobial materials