Propagation of Floquet-Bloch shear waves in viscoelastic composites: analysis and comparison of interface/interphase models for imperfect bonding

The phononic band structure of waves, which travel though composites, results from the geometric and mechanical properties of the materials and from the interaction of the different constituents. In this article, we study two different models to simulate imperfect bonding and their impact on the phononic bands: (a) imperfect bonding is simulated by introducing an artificial interphase constituent with properties which define the bonding quality; (b) imperfect bonding is described by conjugate conditions in the interface, in which the difference in the displacement is proportional to the interfacial stress. Viscoelastic behavior of the constituents has a crucial influence on the traveling signal, and the wave attenuates with increasing viscosity. We study the interaction of the different bonding conditions and the viscoelastic behavior as well as the impact of such interplay on the wave attenuation and dispersion characteristics of the material.Scopu

Exploration of the Zinc Finger Motif in Controlling Activity of Matrix Metalloproteinases

Discovering ways to control the activity of matrix metalloproteinases (MMPs), zinc-dependent enzymes capable of degrading extracellular matrix proteins, is an important field of cancer research. We report here a novel strategy for assembling MMP inhibitors on the basis of oligopeptide ligands by exploring the pattern known as the zinc finger motif. Advanced molecular modeling tools were used to characterize the structural binding motifs of experimentally tested MMP inhibitors, as well as those of newly proposed peptidomimetics, in their zinc-containing active sites. The results of simulations based on the quantum mechanics/molecular mechanics (QM/MM) approach and Car–Parrinello molecular dynamics with QM/MM potentials demonstrate that, upon binding of Regasepin1, a known MMP-9 inhibitor, the Zn²⁺(His₃) structural element is rearranged to the Zn²⁺(Cys₂His₂) zinc finger motif, in which two Cys residues are borrowed from the ligand. Following consideration of the crystal structure of MMP-2 with its inhibitor, the oligopeptide APP-IP, we proposed a new peptidomimetic with two replacements in the substrate, Tyr3Cys and Asp6Cys. Simulations show that this peptide variant blocks an enzyme active site by the Zn²⁺(Cys₂His₂) zinc finger construct. Similarly, a natural substrate of MMP-2, Ace-Gln-Gly ∼ Ile-Ala-Gly-Nme, can be converted to an inhibiting compound by two replacements, Ile by Cys and Gly by the d isomer of Cys, favoring formation of the zinc finger motif

Metal Ions-Stimulated Iron Oxidation in Hydroxylases Facilitates Stabilization of HIF-1α Protein

The exposure of cells to several metal ions stabilizes HIF-1α protein. However, the molecular mechanisms are not completely understood. They may involve inhibition of hydroxylation by either substitution of iron by metal ions or by iron oxidation in the hydroxylases. Here we provide evidence supporting the latter mechanism. We show that HIF-1α stabilization in human lung epithelial cells occurred following exposure to various metal and metalloid ions, including those that cannot substitute for iron in the hydroxylases. In each case addition of the reducing agent ascorbic acid (AA)* abolished HIF-1α protein stabilization. To better understand the role of iron oxidation in hydroxylase inhibition and to define the role of AA in the enzyme recovery we applied molecular modeling techniques. Our results indicate that the energy required for iron substitution by Ni(II) in the enzyme is high and unlikely to be achieved in a biological system. Additionally, computer modeling allowed us to identify a tridentate coordination of AA with the enzyme-bound iron, which explains the specific demand for AA as the iron reductant. Thus, the stabilization of HIF-1α by numerous metal ions that cannot substitute for iron in the enzyme, the alleviation of this effect by AA, and our computer modeling data support the hypothesis of iron oxidation in the hydroxylases following exposure to metal ions