TY - CHAP A1 - Dennstedt, Anne A1 - Gaslain, Fabrice A1 - Bartsch, Marion A1 - Guipont, Vincent A1 - Maurel, Vincent T1 - Crack Morphology in a Columnar Thermal Barrier Coating System N2 - Ceramic layers are used as thermal barrier coatings (TBCs) on metallic substrates. During thermal transients, the thermal expansion mismatch between coating and substrate drives failure of the TBC mainly by interfacial cracking. Laser Shock Adhesion Test (LASAT) provides stresses at the ceramic/metal interface enabling controlled interfacial cracking. For achieving a clear understanding of the influence of local morphology on interfacial toughness, this study aims at characterizing the 3D morphology of a crack at the interface between metal and an EB-PVD TBC having a columnar structure. Cracks were produced by LASAT and documented further in SE and BSE image stacks collected simultaneously during subsequent slice and view operations using a focus ion beam (FIB) and a scanning electron microscope (FIB slice & view). The segmented 3D data gives clear understanding of the columnar structure of the ceramic and of the interaction between the crack and the TBC microstructure. Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:0297-zib-69385 ER - TY - JOUR A1 - Fricke, Mackenzie S. A1 - Frometa, Magalee R. A1 - Kerkhoff, Yannic A1 - Bernhard, Samuel P. A1 - Tahir, Ramat S. A1 - Quaas, Elisa A1 - Totten, William H. A1 - Haag, Rainer A1 - Achazi, Katharina A1 - Cloninger, Mary J. T1 - The toxicity, uptake, and impact on galectin-3 mediated apoptosis of lactose functionalized PAMAM dendrimers JF - Materials Advances N2 - Poly(amidoamine) (PAMAM) dendrimers functionalized with ligands that are designed to interact with biological receptors are important macromolecules for the elucidation and mediation of biological recognition processes. Specifically, carbohydrate functionalized dendrimers are useful synthetic multivalent systems for the study of multivalent protein–carbohydrate interactions. For example, lactose functionalized glycodendrimers can be used to discern the function of galectins, galactoside-binding proteins that are often over-expressed during cancer progression. In order to effectively interpret cancer cellular assays using glycodendrimers, however, their properties in the presence of cells must first be assessed. Macromolecules that are taken up by cells would be expected to have access to many different cell signaling pathways and modes of action that solely extracellular macromolecules cannot utilize. In addition, macromolecules that display cellular toxicity could not be used as drug delivery vehicles. Here, we report fundamental studies of cellular toxicity, viability, and uptake with four generations of lactose functionalized PAMAM dendrimers. In all cases, the dendrimers are readily taken up by the cells but do not display any significant cellular toxicity. The glycodendrimers also increase cellular apoptosis, suggesting that they may abrogate the antiapoptotic protections afforded by galectin-3 to cancer cells. The results reported here indicate that appropriately functionalized PAMAM dendrimers can be used as nontoxic tools for the study and mediation of both extra and intracellular cancer processes. Y1 - 2025 U6 - https://doi.org/10.1039/D4MA00782D VL - 6 SP - 3171 EP - 3184 ER - TY - JOUR A1 - Khatri, Vinod A1 - Boback, Nico A1 - Abdelwahab, Hassan A1 - Niemeyer, Daniela A1 - Palmer, Tahlia M. A1 - Sahoo, Anil Kumar A1 - Kerkhoff, Yannic A1 - Ludwig, Kai A1 - Balci, Dilara A1 - Trimpert, Jakob A1 - Haag, Rainer A1 - Povolotsky, Tatyana L. A1 - Netz, Roland R. A1 - Drosten, Christian A1 - Lauster, Daniel C. A1 - Bhatia, Sumati T1 - Polysialosides outperform sulfated analogs for the inhibition of SARS-CoV-2 JF - Small N2 - Both polysialosides and polysulfates are known to interact with the receptor binding domain (RBD) of the SARS-CoV-2 spike protein. However, a comprehensive site by site analysis of their binding affinities and potential synergistic antiviral effects have not been performed. Here, we report on the synthesis of polysialosides with nanomolar binding affinities to spike proteins of SARS-CoV-2 in solution using microscale thermophoresis (MST). The dendritic polyglycerol based polysialosides dPG500(SA)0.55 and dPG500(SA)0.25, with a dissociation constant Kd of 4.78 nM and 10.85 nM, respectively, bind ~500 times stronger than the high density polysulfated analog dPG500(OSO3Na)0.55, to intact SARS-CoV-2 virus particles or isolated spike protein. In fact, the presence of sulfate groups in a heteromultivalent compound dPG500(SA)0.20(OSO3Na)0.20 weakens the binding to spike proteins. A polycarboxylated analog does not bind to SARS-CoV-2, ruling out that the interaction of polysialoside is simply driven by electrostatic interactions. Furthermore, we found potent nanomolar binding of dPG500(SA)0.55 to SARS-CoV-2 variant B.1.617 (Delta) and B.1.1.529 (Omicron) RBD. Using explicit-solvent all-atom molecular dynamics (MD) simulations and docking studies, we obtain atomistic details on the interaction of different functional groups with the SARS-CoV-2 RBD and their binding affinities. Our data support the conclusion that sialosides interact stronger with RBD than sulfates. Notably, our most affine binder dPG500(SA)0.55 inhibits SARS-CoV-2 (WT, D614G) replication up to 98.6% at low nanomolar concentrations. Y1 - 2025 UR - https://doi.org/10.26434/chemrxiv-2024-8b0gb U6 - https://doi.org/10.1002/smll.202500719 VL - 21 IS - 34 ER -