High Entropy Alloys are inherently complex and span a vast composition space, making their research and discovery challenging. Developing quantitative predictions of their phase selection requires a ...large quantity of consistently determined experimental data. Here, we use combinatorial methods to fabricate and characterize 2478 quinary alloys based on Al and transition metals. All data are publicly available at http://materialsatlasproject.org/. Phase selection can be predicted for considered alloys when combining the content of FCC/BCC elements and the constituents’ atomic size difference. Mining our data reveals that High Entropy Alloys with increasing atomic size difference prefer BCC structure over FCC. This preference is typically overshadowed by other selection motifs, which dominate during close-to-equilibrium processing. Not suggested by the Hume-Rothery rules, this preference originates from the ability of the BCC structure to accommodate a large atomic size difference with lower strain energy penalty which can be practically only realized in High Entropy Alloys.
Display omitted
Ternary amorphous alloys in the magnesium (Mg)-zinc (Zn)-calcium (Ca) and the iron (Fe)-Mg-Zn systems are promising candidates for use in bioresorbable implants and devices. The optimal alloy ...compositions for biomedical applications should be chosen from a large variety of available alloys with best combination of mechanical properties (modulus, strength, hardness) and biological response (
in situ
degradation rates, cell adhesion and proliferation). As a first step towards establishing a database designed to enable such targeted material selection, amorphous alloy composition libraries were fabricated employing a combinatorial magnetron sputtering approach where Mg, Zn, and Ca/Fe are co-deposited from separate sources onto a silicon wafer substrate. Composition analysis using energy dispersive X-ray spectroscopy documented a composition range of ∼15-85 at% Mg, ∼6-55 at% Zn, and ∼5-60 at% Ca for the Mg-Zn-Ca library and ∼26-84 at% Mg, ∼10-61 at% Zn, and ∼7-55 at% Fe for the Fe-Mg-Zn library. X-ray diffraction measurements established that amorphous alloys (
i.e.
, glasses) form in almost the entire range of composition at the high cooling rates during sputtering for both alloy libraries. Finally, the effective material modulus, the Oliver-Pharr hardness, and the yield strength values obtained using nanoindentation reveal a wide range of mechanical properties within both systems.
High throughput discovery of amorphous bioresorbable alloys. Top: combinatorial sputtering setup. Bottom: composition of libraries deposited on silicon (Si) wafers for (a) magnesium (Mg)-zinc (Zn)-calcium (Ca) and the (b) iron (Fe)-Mg-Zn systems.
Display omitted
•Stretch blow molding provides a new processing method to fabricate high aspect ratio BMG complex shapes.•Shapes requiring strains of over 2000% can be achieved.•Thickness ...distribution can be quantified and estimated through a mathematical model.•Amorphous state with associated high mechanical properties can be maintained throughout the stretch blow molding process.
Bulk metallic glasses (BMGs) exhibit remarkable mechanical properties, such as high strength and elasticity, which is often paired with fracture toughness. Their supercooled liquid region gives rise to plastic-like processing and suggests parts and shapes that can otherwise not be obtained for crystalline metals. However, current processing techniques only allow for limited options in terms of geometry, thicknesses uniformity, and shape complexity. Here we introduce a new processing technique, “stretch blow molding,” to expand the range of possible parts and increase the available geometries that can be fabricated with BMGs. Additionally, a model is derived that allows for the quantification and prediction of stretch blow molding and provides insight into its potential use and limitations. We demonstrate that with stretch blow molding overall strains exceeding 2000% are achievable, compared to the previously reported ∼150% of blow molding. With the ability to stretch blow mold shapes that were previously unachievable with any other metal fabrication technique in a fast and economical manner, and the superb properties of BMGs, we look forward to a broad commercial adaptation of this technique.
We consider a broad range of 13 BMGs from different alloy systems to represent the material class of bulk metallic glasses (BMGs) and characterize their fracture toughness. To determine the effect of ...composition on the fracture toughness within one alloy system, we consider alloys in Zr-Al-Ni-Cu and Pd-Ni-Cu-P BMG forming alloy systems, specifically Zrx(Al0.25Ni0.25Cu0.5)100-x (at.%) and Pdx(NiCu2)(80-x)/3P20. Sample preparation follows a thermoplastic forming based method ensuring constant fictive temperature, which allows us to eliminate extrinsic effects and detangle the effect of fictive temperature and alloy chemistry on the fracture toughness. We found that fracture toughness varies significantly with composition, even in a non-monotonic way. Within one alloy system, fracture toughness correlates closely with the ratio of shear modulus over bulk modulus. Such correlation however is not present when comparing BMGs across alloy systems. Observed behavior suggests that shear modulus and bulk modulus serves as an incomplete proxy describing the BMGs ability to resist shear and cavitation. Further, our results reveal a general inverse correlation between fracture toughness and glass forming ability suggesting a trade-off of both desired properties. Such trade-off is not necassary present in metal-metalloid containing BMGs, where our results reveal a possibility to optimize alloys for both GFA and fracture toughness simultaneously.
Display omitted
High throughput discovery of amorphous bioresorbable alloys. Top: combinatorial sputtering setup. Bottom: composition of libraries deposited on silicon (Si) wafers for (a) magnesium (Mg)–zinc ...(Zn)–calcium (Ca) and the (b) iron (Fe)–Mg–Zn systems.
Today, aircraft composite structures are generally over-dimensioned to avoid catastrophic failure by unseen damages. This leads to a higher system weight and therefore an unwanted increase in ...greenhouse gas emissions. To reduce this parasitic mass, load monitoring can play an important role in damage detection. Additionally, the weight and volume of future aircraft structures can also be reduced by energy storing and load carrying structures: so-called power composites. In this study a novel method of combining both approaches for maximum weight reduction is shown. This is achieved by using power composites as load monitoring sensors and energy suppliers. Therefore, supercapacitors are integrated into fiber reinforced polymers and are then used to investigate the mechanical load influence. By using four-point bending experiments and in situ electrochemical impedance spectroscopy, a strong relation between the mechanical load and the electrochemical system is found and analyzed using a model. For the first time, it is possible to detect small strain values down to 0.2% with a power composite. This strain is considerably lower than the conventional system load. The developed model and the impedance data indicate the possibility of using the composite as an energy storage as well as a strain sensor.
The bacterial type VI secretion system is a multicomponent molecular machine directed against eukaryotic host cells and competing bacteria. It consists of a contractile tubule that is attached to a ...membrane protein complex. Upon tubule contraction, a needle is ejected into target cells to translocate toxic effectors into the cell. Due to structural and functional homologies of several proteins of the secretion system to proteins of contractile bacteriophage tails, the system is generally described as an inverted phage tail. Following this analogy, the secretion process is driven by energy stored in the elongated conformation of the Type VI secretion tubule for which also partial structural homology to bacteriophage tail sheath proteins has been predicted. However, this prediction has not been corroborated by structural data so far. The AAA+ ATPase ClpV plays an important role in the secretion process, as it disassembles the contracted tubule, putatively for recycling of the complex. Even though the binding site for ClpV has been identified in VipB, the molecular mechanism which recruits the ATPase specifically to the contracted tubule is not known yet.
In a collaborative project with PD Dr. Axel Mogk and colleagues at the DKFZ Heidelberg and the group of Dr. Franz Herzog at the Gene Center Munich, we investigate the structure of the Vibrio cholerae Type VI secretion tubule consisting of the proteins VipA and VipB. We employ a hybrid methods approach of cryo electron microscopic 3D reconstruction and electron microscopic and biochemical labeling techniques supported by cross-linking mass spectrometry to develop a structural model of VipA and VipB in the tubule. We are able to resolve the three-dimensional structure of the helical VipA/B tubule up to 6 Å which allows us to locate secondary structure elements. We describe the arrangement of VipA and VipB in the asymmetric unit and show that the architecture of the tubule is mainly defined by contacts between C-terminal domains of VipB which are structurally similar to domain IV of viral tail sheath proteins. By comparison to the T4 bacteriophage tail sheath, we suggest that these structurally homologous parts mediate the common function of contraction. Additionally, the VipA/B tubule has been adapted towards efficient recycling of contracted Type VI secretion systems. VipB is equipped with a specific four-helix bundle N-terminal domain which carries the ClpV binding motif. Also for VipA, no correspondency to any other known structural part of a phage-like contractile system is found. We propose that it serves as a chaperone for VipB. Based on the observed structural homologies between the T4 phage tail sheath protein and VipB, we model the elongated state of the VipA/B tubule using known low resolution structures of the elongated T4 phage tail. Furthermore, we suggest a molecular mechanism for Type VI secretion tubule recycling. In the elongated state of the tubule, the VipB N-terminal domain is hidden in the tubule wall, making the ClpV binding motif inaccessible for the ATPase. Therefore, ClpV-mediated recycling of the tubule is restricted to its contracted state.
Das bakterielle Typ-VI-Sekretionssystem ist eine aus vielen unterschiedlichen Teilen bestehende molekulare Maschine, die gegen eukaryotische Wirtszellen und konkurrierende Bakterien gerichtet ist. Sie besteht aus einem kontraktionsfähigen Tubulus, welcher mit einem Komplex aus Membranproteinen verbunden ist. Durch Kontraktion des Tubulus wird eine Nadel in eine Zielzelle gestoßen, um Gifte in die Zelle zu injizieren. Aufgrund von strukturellen und funktionalen Homologien von einigen Proteinen des Sekretionssystems zu Proteinen des kontraktionsfähigen Bakteriophagenschwanzes wird das System allgemein als umgedrehter Phagenschwanz beschrieben. In dieser Analogie wird der Sekretionsprozess durch die in der elongierten Konformation des Typ-VI-Sekretionstubulus gespeicherte Energie angetrieben. Für ihn wurde auch eine teilweise strukturelle Homologie zum Mantelprotein des Bakteriophagenschwanzes vorhergesagt, aber nie durch strukturelle Daten belegt. Die AAA+ ATPase ClpV spielt eine wichtige Rolle im Sekretionsprozess, da sie den kontrahierten Tubulus zerlegt, vermutlich zur Wiederverwertung des Komplexes. Obwohl die ClpV-Bindestelle in VipB bereits identifiziert wurde, ist der molekulare Mechanismus, der die ATPase ausschließlich an kontrahierten Tubuli binden lässt, unbekannt.
In einem Kollaborationsprojekt mit PD Dr. Axel Mogk und Mitarbeitern am DKFZ Heidelberg und der Gruppe von Dr. Franz Herzog am Gen-Zentrum München, untersuchen wir die Struktur des Typ-VI-Sekretionstubulus aus Vibrio cholerae, welcher aus den Proteinen VipA und VipB besteht. Wir verbinden in unserem Ansatz die 3D-Rekonstruktion aus kryo-elektronenmikroskopischen Bildern mit elektronenmikroskopischen und biochemischen Markierungsmethoden und entwickeln ein Strukturmodell von VipA und VipB im Tubulus, welches durch den massenspektrometrischen Nachweis chemisch quervernetzter Peptide gestützt wird. Wir können die dreidimensionale Struktur des helikalen VipA/B-Tubulus bis auf 6 Å auflösen, was es uns ermöglicht, Sekundärstrukturelemente zu lokalisieren. Wir beschreiben die Anordnung von VipA und VipB in der asymmetrischen Untereinheit und zeigen, dass die Architektur des Tubulus hauptsächlich durch Kontakte zwischen C-terminalen Domänen von VipB bestimmt wird, welche strukturell der Domäne IV der Mantelproteine des Bakteriophagenschwanzes ähneln. Der Vergleich mit dem Mantel des T4 Bakteriophagenschwanzes, führt uns zu dem Vorschlag, dass diese struktur-homologen Bestandteile die gleiche Funktion in der Kontraktion besitzen. Zusätzlich ist der VipA/B-Tubulus einer effizienten Wiederverwertung des Typ-VI-Sekretionssystems angepasst. VipB besitzt eine spezielle N-terminale Domäne, die aus einem Bündel aus vier Helices besteht und das Erkennungsmotiv für ClpV trägt. Für VipA finden wir ebenfalls keine Entsprechung zu anderen phagen-ähnlichen kontraktionsfähigen Systemen. Unserer Ansicht nach dient es als Chaperon für VipB. Basierend auf den beobachteten Strukturhomologien zwischen dem Mantelprotein des T4 Bakteriophagenschwanzes und VipB, entwerfen wir unter der Verwendung von niedrig aufgelösten Strukturen des elongierten T4 Phagenschwanzes ein Modell des elongierten Zustands des VipA/B-Tubulus. Des Weiteren schlagen wir einen molekularen Mechanismus für die Wiederverwertung des Typ-VI-Sekretionstubulus vor. Im elongierten Zustand des Tubulus ist die N-terminale Domäne von VipB in der Wand des Tubulus versteckt. Daher ist das ClpV-Erkennungsmotiv für die ATPase nicht zugänglich und der Abbau des Tubulus durch ClpV auf seinen kontrahierten Zustand beschränkt.
Monoclonal antibody (mAb)-based therapeutics often require high-concentration formulations. Unfortunately, highly concentrated antibody solutions often have biophysical properties that are ...disadvantageous for therapeutic development, such as high viscosity, solubility limitations, precipitation issues, or liquid–liquid phase separation. In this work, we present a computational rational design principle for improving the thermodynamic stability of mAb solutions through targeted point mutations. Two publicly available IgG1 monoclonal antibodies that exhibit high viscosity at high concentrations were used as model systems. Guided by a computationally efficient approach that combines molecular dynamics simulations with three-dimensional reference interaction site model theory, point mutations of charged residues were introduced in the variable Fv regions in such a manner that the hydration free energy was optimized. Two selected point mutants were then produced by transient expression and characterized experimentally. Both engineered mAbs have reduced viscosity at high concentration, less negative second virial coefficient, and improved solubility compared to the respective wild-types. The results obtained with the suggested straightforward design principle underline the relevance of solvation effects for understanding, and ultimately optimizing, the properties of highly concentrated mAb solutions, with possible implications also for other biomolecular systems.
We report the x-ray crystal structure of intact, full-length human immunoglobulin (IgG4) at 1.8 Å resolution. The data for IgG4 (S228P), an antibody targeting the natriuretic peptide receptor A, show ...a previously unrecognized type of Fab-Fc orientation with a distorted λ-shape in which one Fab-arm is oriented toward the Fc portion. Detailed structural analysis by x-ray crystallography and molecular simulations suggest that this is one of several conformations coexisting in a dynamic equilibrium state. These results were confirmed by small angle x-ray scattering in solution. Furthermore, electron microscopy supported these findings by preserving molecule classes of different conformations. This study fosters our understanding of IgG4 in particular and our appreciation of antibody flexibility in general. Moreover, we give insights into potential biological implications, specifically for the interaction of human anti-natriuretic peptide receptor A IgG4 with the neonatal Fc receptor, Fcγ receptors, and complement-activating C1q by considering conformational flexibility.
PDF
