2019, Yildiz, Deniz, Baumann, Christoph, Mikosch, Annabel, Kuehne, Alexander J.C., Herrmann, Andreas, Göstl, Robert

The development of methods to detect damage in macromolecular materials is of paramount importance to understand their mechanical failure and the structure–property relationships of polymers. Mechanofluorophores are useful and sensitive molecular motifs for this purpose. However, to date, tailoring of their optical properties remains challenging and correlating emission intensity to force induced material damage and the respective events on the molecular level is complicated by intrinsic limitations of fluorescence and its detection techniques. Now, this is tackled by developing the first stress-sensing motif that relies on photon upconversion. By combining the Diels–Alder adduct of a π-extended anthracene with the porphyrin-based triplet sensitizer PtOEP in polymers, triplet–triplet annihilation photon upconversion of green to blue light is mechanochemically activated in solution as well as in the solid state. © 2019 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.

2019, Chakraborty, Gurudas, Balinin, Konstantin, Portale, Giuseppe, Loznik, Mark, Polushkin, Evgeny, Weil, Tanja, Herrmann, Andreas

Chemically modified nucleic acids have long served as a very important class of bio-hybrid structures. In particular, the modification with PEG has advanced the scope and performance of oligonucleotides in materials science, catalysis and therapeutics. Most of the applications involving pristine or modified DNA rely on the potential of DNA to form a double-stranded structure. However, a substantial requirement for metal-cations to achieve hybridization has restricted the range of applications. To extend the applicability of DNA in salt-free or low ionic strength aqueous medium, we introduce noncovalent DNA-PEG constructs that allow canonical base-pairing between individually PEGylated complementary strands resulting in a double-stranded structure in salt-free aqueous medium. This method relies on grafting of amino-terminated PEG polymers electrostatically onto the backbone of DNA, which results in the formation of a PEG-envelope. The specific charge interaction of PEG molecules with DNA, absolute absence of metal ions within the PEGylated DNA molecules and formation of a double helix that is significantly more stable than the duplex in an ionic buffer have been unequivocally demonstrated using multiple independent characterization techniques. This journal is © The Royal Society of Chemistry.

2019, Huo, Shuaidong, Gong, Ningqiang, Jiang, Ying, Chen, Fei, Guo, Hongbo, Gan, Yaling, Wang, Zhisen, Herrmann, Andreas, Liang, Xing-Jie

The development of an efficient delivery system for enhanced and controlled gene interference–based therapeutics is still facing great challenges. Fortunately, the flourishing field of nanotechnology provides more effective strategies for nucleic acid delivery. Here, the triplex-forming oligonucleotide sequence and its complementary strand were used to mediate self-assembly of ultrasmall gold nanoparticles. The obtained sunflower-like nanostructures exhibited strong near-infrared (NIR) absorption and photothermal conversion ability. Upon NIR irradiation, the large-sized nanostructure could disassemble and generate ultrasmall nanoparticles modified with c-myc oncogene silencing sequence, which could directly target the cell nucleus. Moreover, the controlled gene silencing effect could be realized by synergistically controlling the preincubation time with the self-assembled nanostructure (in vitro and in vivo) and NIR irradiation time point. This study provides a new approach for constructing more efficient and tailorable nanocarriers for gene interference applications

2019, Huo, Shuaidong, Li, Hongyan, Boersma, Arnold J., Herrmann, Andreas

DNA is more than a carrier of genetic information: It is a highly versatile structural motif for the assembly of nanostructures, giving rise to a wide range of functionalities. In this regard, the structure programmability is the main advantage of DNA over peptides, proteins, and small molecules. DNA amphiphiles, in which DNA is covalently bound to synthetic hydrophobic moieties, allow interactions of DNA nanostructures with artificial lipid bilayers and cell membranes. These structures have seen rapid growth with great potential for medical applications. In this Review, the current state of the art of the synthesis of DNA amphiphiles and their assembly into nanostructures are first summarized. Next, an overview on the interaction of these DNA amphiphiles with membranes is provided, detailing on the driving forces and the stability of the interaction. Moreover, the interaction with cell surfaces in respect to therapeutics, biological sensing, and cell membrane engineering is highlighted. Finally, the challenges and an outlook on this promising class of DNA hybrid materials are discussed.

2019, Smit, Jochem H., van der Velde, Jasper H. M., Huang, Jingyi, Trauschke, Vanessa, Henrikus, Sarah S., Chen, Si, Eleftheriadis, Nikolaos, Warszawik, Eliza M., Herrmann, Andreas, Cordes, Thorben

While buffer cocktails remain the most commonly used method for photostabilization and photoswitching of fluorescent markers, intramolecular triplet-state quenchers emerge as an alternative strategy to impart fluorophores with ‘self-healing’ or even functional properties such as photoswitching. In this contribution, we evaluated combinations of both approaches and show that inter- and intramolecular triplet-state quenching processes compete with each other. We find that although the rate of triplet-state quenching is additive, the photostability is limited by the faster pathway. Often intramolecular processes dominate the photophysical situation for combinations of covalently-linked and solution-based photostabilizers and photoswitching agents. Furthermore we show that intramolecular photostabilizers can protect fluorophores from reversible off-switching events caused by solution-additives, which was previously misinterpreted as photobleaching. Our studies also provide practical guidance for usage of photostabilizer–dye conjugates for STORM-type super-resolution microscopy permitting the exploitation of their improved photophysics for increased spatio-temporal resolution. Finally, we provide evidence that the biochemical environment, e.g., proximity of aromatic amino-acids such as tryptophan, reduces the photostabilization efficiency of commonly used buffer cocktails. Not only have our results important implications for a deeper mechanistic understanding of self-healing dyes, but they will provide a general framework to select label positions for optimal and reproducible photostability or photoswitching kinetics in different biochemical environments.

2019, Ma, Chao, Su, Juanjuan, Sun, Yao, Feng, Yang, Shen, Nolan, Li, Bo, Liang, Yingxia, Yang, Xintong, Wu, Hui, Zhang, Hongjie, Herrmann, Andreas, Tanzi, Rudolph E., Liu, Kai, Zhang, Can

Alzheimer's disease (AD) is a neurodegenerative disorder and the primary cause of age-related dementia. The etiology of AD is complex and has not been completely elucidated. Herein, we report that treatment with elastin-like polypeptides (ELPs), a component of the brain extracellular matrix (ECM), significantly increased the levels of AD-related amyloid-β peptides (Aβ) both in vitro and in vivo. Regarding the molecular mechanism(s), the upregulation of Aβ levels was related to increased proteolytic processing of the amyloid precursor protein. Furthermore, nesting tests demonstrated that the ELP-treated animals showed significant neurobehavioral deficits with cognitive impairment. These results suggest that the elastin is associated with AD-related pathological and behavioral changes. This finding presents a new aspect for Alzheimer's amyloidosis event and provides a great promise in developing ELP-based model systems to better understand the pathogenesis of AD. © 2019

2019, Smit, Jochem H., Li, Yichen, Warszawik, Eliza M., Herrmann, Andreas, Cordes, Thorben, Gilestro, Giorgio F

Single-molecule fluorescence microscopy studies of bacteria provide unique insights into the mechanisms of cellular processes and protein machineries in ways that are unrivalled by any other technique. With the cost of microscopes dropping and the availability of fully automated microscopes, the volume of microscopy data produced has increased tremendously. These developments have moved the bottleneck of throughput from image acquisition and sample preparation to data analysis. Furthermore, requirements for analysis procedures have become more stringent given the demand of various journals to make data and analysis procedures available. To address these issues we have developed a new data analysis package for analysis of fluorescence microscopy data from rod-like cells. Our software ColiCoords structures microscopy data at the single-cell level and implements a coordinate system describing each cell. This allows for the transformation of Cartesian coordinates from transmission light and fluorescence images and single-molecule localization microscopy (SMLM) data to cellular coordinates. Using this transformation, many cells can be combined to increase the statistical power of fluorescence microscopy datasets of any kind. ColiCoords is open source, implemented in the programming language Python, and is extensively documented. This allows for modifications for specific needs or to inspect and publish data analysis procedures. By providing a format that allows for easy sharing of code and associated data, we intend to promote open and reproducible research. The source code and documentation can be found via the project’s GitHub page.