Erythropoietin deficiency is an extensively researched cause of renal anemia. The etiology and consequences of shortened red blood cell (RBC) life span in chronic kidney disease (CKD) are less well understood. Traversing capillaries requires RBC geometry changes, a process enabled by adaptions of the cytoskeleton. These changes are mediated by transient activation of the mechanosensory Piezo1 channel, resulting in calcium influx. Importantly, prolonged Piezo1 activation shortens RBC life span, presumably through activation of calcium‐dependent intracellular pathways triggering RBC death. Two Piezo1‐activating small molecules, Jedi1 and Jedi2, share remarkable structural similarities with 3‐carboxy‐4‐methyl‐5‐propyl‐2‐furanpropanoic acid (CMPF), a uremic retention solute cleared by the healthy kidney. We hypothesize that in CKD the accumulation of CMPF leads to prolonged activation of Piezo1 (similar in effect to Jedi1 and Jedi2), thus reducing RBC life span. This hypothesis can be tested through bench experiments and, ultimately, by studying the effect of CMPF removal on renal anemia.

Integrins, as transmembrane heterodimeric receptors, have important functions in cell adhesion, migration, proliferation, survival apoptosis and signal transduction, in many physio- as well as pathophysiological settings. Characterisation of integrins and their ligand/antagonist binding is notoriously difficult, due to high integrin redundancy and ubiquity. Bypassing the intrinsic difficulties of cell-based integrin expression, purification and reconstitution, we present for the first time the synthesis of a heterodimeric integrin receptor and its assembly into a block-copolymeric membrane mimic. We present comprehensive data to demonstrate the synthesis of functionally active integrin αv β3, generated by in vitro membrane-assisted protein synthesis (iMAPS). This work represents the first step towards a robust and adaptable polymer-based platform for characterisation of integrin-ligand interactions.

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Silica-based nanoparticles (SiNPs) are presented to harvest complex membrane proteins, which have been embedded into unilammelar polymersomes via in vitro membrane assisted protein synthesis (iMAP). Size-optimized SiNPs have been surface-modified with polymer-targeting antibodies, which are employed to harvest the protein-containing polymersomes. The polymersomes mimic the cellular membrane. They are chemically defined and preserve their structural-functional integrity as virtually any membrane protein species can be synthesized into such architecture via the ribosomal context of a cellular lysate. The SiNPs resemble 'heavy leg irons' catching the polymersomes in order to enable gravity-based generic purification and concentration of such proteopolymersomes from the crude mixture of cellular lysates.

Semiconductor quantum dots (QDs) are widely used for optical applications and bioimaging. In comparison to organic dyes used for fluorescent labeling, QDs exhibit very high photostability and can be further surface modified. Equipping QDs with magnetic properties (mQDs) makes it possible to combine fluorescence and magnetic resonance imaging analyses. For this purpose, we have prepared water-dispersible and magnetic CdTe/ZnS mQDs, whereby ferrous ions are selectively incorporated in either their cores or their shells. This study aims at understanding the differences in optical, structural, and magnetic properties between these core- and shell-doped mQDs. Field-dependent isothermal magnetic susceptibility measurements show that shell-doped mQDs exhibit paramagnetic and their core-doped equivalents super­paramagnetic behavior near room temperature. Shell doping results in about 1.7 times higher photoluminescence quantum yields and 1.4 times higher doping efficiency than core doping. X-ray diffraction patterns reveal that core doping leads to defects in the lattice and hence to a severe decrease in crystallinity, whereas shell doping has no significant impact on the crystal structure and consequently fewer disadvantages regarding the mQD’s quantum yield. These selective doping approaches, particularly shell doping, allow for the tailored design of paramagnetic QDs having modifiable and biocompatible particle surfaces. The organic ligandsin this study N-acetyl-l-cysteinesufficiently prevent leakage of toxic metal ions, as shown by cytotoxicity assays with HepG2 cells. Confocal laser scanning microscopy shows that mQDs are internalized by these cells and accumulated near their nuclei. This study shows that biocompatible, fluorescent, and paramagnetic QDs are promising photostable labels for multimodal bioimaging.

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We present a potential theranostic delivery platform based on the amphiphilic diblock copolymer polybutadiene-block-poly (ethylene oxide) combining covalent fluorescent labeling and membrane incorporation of superparamagnetic iron oxide nanoparticles for multimodal imaging. A simple self-assembly and labeling approach to create the fluorescent and magnetic vesicles is described. Cell uptake of the densely PEGylated polymer vesicles could be altered by surface modifications that vary surface charge and accessibility of the membrane active species. Cell uptake and cytotoxicity were evaluated by confocal microscopy, transmission electron microscopy, iron content and metabolic assays, utilizing multimodal tracking of membrane fluorophores and nanoparticles. Cationic functionalization of vesicles promoted endocytotic uptake. In particular, incorporation of cationic lipids in the polymersome membrane yielded tremendously increased uptake of polymersomes and magnetopolymersomes without increase in cytotoxicity. Ultrastructure investigations showed that cationic magnetopolymersomes disintegrated upon hydrolysis, including the dissolution of incorporated iron oxide nanoparticles. The presented platform could find future use in theranostic multimodal imaging in vivo and magnetically triggered delivery by incorporation of thermorepsonsive amphiphiles that can break the membrane integrity upon magnetic heating via the embedded superparamagnetic nanoparticles.

Nanomaterials in research, industry and the environmentcase studies for nanoscopic reference materialsAbstract Engineered nanomaterials have established themselves as a staple in industry, and have paved the way for the development of new products. On one hand, their size and specific, highly chemically reactive surfaces make nanomaterials promising candidates in terms of their range of applications. On the other, it's virtually impossible to make any universally valid statements on their potential effects on human beings or the environment.The difficulty of assessing the safety of these innovative materials, which are often made of complex compositions, is compounded by the fact that not only the chemical species and the amount/ dosage but also further physical-chemical parameters like the particle shape, structure, specific surface characteristics, size and size distribution are important aspects. As such, it is currently extremely difficult to take into account potential transformation processes like the aggregation into larger clusters or dissolution into ionic components, and to differentiate between nanomaterialspecific and nonspecific effects. In addition, nano-scale reference materials and nanomaterials that can be found in complex environmental samples are currently in short supply. Accordingly, the standardized methods and testing techniques currently in use must be refined and adapted. In response to these challenges, this article proposes new approaches to differentiating between synthetic nanomaterials and their naturally occurring counterparts, illustrating them on the basis of an environmentally relevant sample application.