Modelling bispecific monoclonal antibody interaction with two cell membrane targets indicates the importance of surface diffusion

We have developed a mathematical framework for describing a bispecific monoclonal antibody interaction with two independent membrane-bound targets that are expressed on the same cell surface. The bispecific antibody in solution binds either of the two targets first, and then cross-links with the second one whilst on the cell surface, subject to rate-limiting lateral diffusion step within the lifetime of the monovalently engaged antibody-antigen complex. At experimental densities, only a small fraction of the free targets is expected to lie within the reach of the antibody binding sites at any time. Using ordinary differential equation and Monte Carlo simulation-based models, we validated this approach against an independently published anti-CD4/CD70 DuetMab experimental data set. As a result of dimensional reduction, the cell surface reaction is expected to be so rapid that, in agreement with the experimental data, no monovalently bound bispecific antibody binary complexes accumulate until cross-linking is complete. The dissociation of the bispecific antibody from the ternary cross-linked complex is expected to be significantly slower than that from either of the monovalently bound variants. We estimate that the effective affinity of the bivalently bound bispecific antibody is enhanced for about four orders of magnitude over that of the monovalently bound species. This avidity enhancement allows for the highly specific binding of anti-CD4/CD70 DuetMab to the cells that are positive for both target antigens over those that express only one or the other We suggest that the lateral diffusion of target antigens in the cell membrane also plays a key role in the avidity effect of natural antibodies and other bivalent ligands in their interactions with their respective cell surface receptors

Synthesis and characterization of the bioactive ternary SiO2-CaO-P2O5 Bioglass

In this paper, we present our results on the synthesis and characterization of silicon dioxide or silica calcium oxide and phosphorus pentoxide (SiO2-CaO-P2O5) glass by means of the sol-gel method where previous works have used tetraethyl orthosilicate (TEOS) as SiO2 precursor, but here we are using the commercialized aerosol SiO2. Indeed, our synthesis of this gel-glass nanocomposite was carried out using the aerosol SiO2, calcium nitrate tetrahydrate (CaNO3.4H2O) and sodium hydrogenphosphate (Na2HPO4) as precursors of SiO2, CaO and P2O5 respectively. The characterization was carried out by infrared spectroscopy (FTIR), X-ray diffraction (XRD), and field emission scanning electron microscopy (FESEM) to study their chemical bonding, structural and morphological properties of the resulting amorphous glass. These techniques conducted us to detect the chemical modifications induced by modifying the Ca/P molar ratio. In addition, the thermal properties of the synthesized gel-glass materials were studied using thermogravimetric and differential thermal analysis (TG/DTA). The results revealed that the glass transition temperature is around 600degC, with the aim to convert them into ceramic powders through calcinations treatment. The results gave us porous bioactive materials that can be suitable for many applications such as prolonged-release drug or bone tissue repairing.nbspnbs

Combined Proteomic and Molecular Approaches for Cloning and Characterization of Copper–Zinc Superoxide dismutase (Cu, Zn-SOD2) from Garlic (Allium sativum)

International audienc