Synthesis and Characterization of a Novel Biocompatible Alloy, ti-nb-zr-ta-sn

Many current-generation biomedical implants are fabricated from the Ti-6Al-4V alloy because it has many attractive properties, such as low density and biocompatibility. However, the elastic modulus of this alloy is much larger than that of the surrounding bone, leading to bone resorption and, eventually, implant failure. In the present study, we synthesized and performed a detailed analysis of a novel low elastic modulus Ti-based alloy (Ti-28Nb-5Zr-2Ta-2Sn (TNZTS alloy)) using a variety of methods, including scanning electron microscopy, transmission electron microscopy, X-ray diffraction, and tensile test. Additionally, the in vitro biocompatibility of the TNZTS alloy was evaluated using SCP-1, SaOs-2, and THP-1 cell lines and primary human osteoblasts. Compared to Ti-6Al-4V, the elastic modulus of TNZTS alloy was significantly lower, while measures of its in vitro biocompatibility are comparable. O2 plasma treatment of the surface of the alloy significantly increased its hydrophilicity and, hence, its in vitro biocompatibility. TNZTS alloy specimens did not induce the release of cytokines by macrophages, indicating that such scaffolds would not trigger inflammatory responses. The present results suggest that the TNZTS alloy may have potential as an alternative to Ti-6Al-4V. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.Funding: The experimental work was funded by the State Assignment (Russian Federation, Grant No. 0836-2020-0020) and DAAD together with the Ministry of Education and Science of the Russian Federation within the Michael Lomonosov Program (project No. 57447934)

Meta-stability of the hemifusion intermediate induced by glycosylphosphatidylinositol-anchored influenza hemagglutinin.

Fusion between influenza virus and target membranes is mediated by the viral glycoprotein hemagglutinin (HA). Replacement of the transmembrane domain of HA with a glycosylphosphatidylinositol (GPI) membrane anchor allows lipid mixing but not the establishment of cytoplasmic continuity. This observation led to the proposal that the fusion mechanism passes through an intermediate stage corresponding to hemifusion between outer monolayers. We have used confocal fluorescence microscopy to study the movement of probes for specific bilayer leaflets of erythrocytes fusing with HA-expressing cells. N-Rh-PE and NBD-PC were used for specific labeling of the outer and inner membrane leaflet, respectively. In the case of GPI-HA-induced fusion, different behaviors of lipid transfer were observed, which include 1) exclusive movement of N-Rh-PE (hemifusion), 2) preferential movement of N-Rh-PE relative to NBD-PC, and 3) equal movement of both lipid analogs. The relative population of these intermediate states was dependent on the time after application of a low pH trigger for fusion. At early time points, hemifusion was more common and full redistribution of both bilayers was rare, whereas later full redistribution of both probes was frequently observed. In contrast to wild-type HA, the latter was not accompanied by mixing of the cytoplasmic marker Lucifer Yellow. We conclude that 1) the GPI-HA-mediated hemifusion intermediate is meta-stable and 2) expansion of an aqueous fusion pore requires the transmembrane and/or cytoplasmic domain of HA

Structure and topology of the influenza virus fusion peptide in lipid bilayers.

The secondary structure of a 20-amino acid length synthetic peptide corresponding to the N terminus of the second subunit of hemagglutinin (HA2) of influenza virus A/PR8/34 and its interaction with phospholipid bilayers are investigated using ESR, Fourier transform infrared (FTIR), and CD spectroscopy. N-terminal spin labeling of the peptide did not affect the secondary structure of the peptide either in solution or when bound to liposomes as revealed by FTIR and CD spectroscopy. ESR spectra show that the mobility of the labeled peptide is dramatically restricted in the presence of phosphatidylcholine liposomes, suggesting a strong binding to the lipid membranes. The N terminus of the peptide penetrates into the membrane and is located within the hydrophobic core. We find an oblique insertion of the peptide into the lipid bilayer with an angle of about 45 degrees between helix axis and membrane plane using FTIR spectroscopy. No gross changes of the peptide's orientation, motion, and secondary structure were observed between pH 7.4 and pH 5.0. A model of the insertion of the fusion sequence of HA2 into a lipid bilayer is presented taking into account recent investigations on the low pH conformation of HA2 (Bullough, P. A. Hughson, F. M. Skehel, J. J. and Wiley, D. C. (1994) Nature 371, 37-43).Comparative StudyJournal Articleinfo:eu-repo/semantics/publishe