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DNA Nanotechnology Enters Cell Membranes
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.
De novo rational design of a freestanding, supercharged polypeptide, proton-conducting membrane
2020, Ma, Chao, Dong, Jingjin, Viviani, Marco, Tulini, Isotta, Pontillo, Nicola, Maity, Sourav, Zhou, Yu, Roos, Wouter H., Liu, Kai, Herrmann, Andreas, Portale, Giuseppe
Proton translocation enables important processes in nature and man-made technologies. However, controlling proton conduction and fabrication of devices exploiting biomaterials remains a challenge. Even more difficult is the design of protein-based bulk materials without any functional starting scaffold for further optimization. Here, we show the rational design of proton-conducting, protein materials exceeding reported proteinaceous systems. The carboxylic acid-rich structures were evolved step by step by exploring various sequences from intrinsically disordered coils over supercharged nanobarrels to hierarchically spider β sheet containing protein-supercharged polypeptide chimeras. The latter material is characterized by interconnected β sheet nanodomains decorated on their surface by carboxylic acid groups, forming self-supportive membranes and allowing for proton conduction in the hydrated state. The membranes showed an extraordinary proton conductivity of 18.5 ± 5 mS/cm at RH = 90%, one magnitude higher than other protein devices. This design paradigm offers great potential for bioprotonic device fabrication interfacing artificial and biological systems. Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).
Ultra-strong bio-glue from genetically engineered polypeptides
2021, Ma, Chao, Sun, Jing, Li, Bo, Feng, Yang, Sun, Yao, Xiang, Li, Wu, Baiheng, Xiao, Lingling, Liu, Baimei, Petrovskii, Vladislav S., Zhang, Jinrui, Wang, Zili, Li, Hongyan, Zhang, Lei, Li, Jingjing, Wang, Fan, GÓ§stl, Robert, Potemkin, Igor I., Chen, Dong, Zeng, Hongbo, Zhang, Hongjie, Liu, Kai, Herrmann, Andreas
The development of biomedical glues is an important, yet challenging task as seemingly mutually exclusive properties need to be combined in one material, i.e. strong adhesion and adaption to remodeling processes in healing tissue. Here, we report a biocompatible and biodegradable protein-based adhesive with high adhesion strengths. The maximum strength reaches 16.5 ± 2.2 MPa on hard substrates, which is comparable to that of commercial cyanoacrylate superglue and higher than other protein-based adhesives by at least one order of magnitude. Moreover, the strong adhesion on soft tissues qualifies the adhesive as biomedical glue outperforming some commercial products. Robust mechanical properties are realized without covalent bond formation during the adhesion process. A complex consisting of cationic supercharged polypeptides and anionic aromatic surfactants with lysine to surfactant molar ratio of 1:0.9 is driven by multiple supramolecular interactions enabling such strong adhesion. We demonstrate the glue’s robust performance in vitro and in vivo for cosmetic and hemostasis applications and accelerated wound healing by comparison to surgical wound closures.
Gold-DNA nanosunflowers for efficient gene silencing with controllable transformation
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
ColiCoords: A Python package for the analysis of bacterial fluorescence microscopy data
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.