CONICET | Buscador de Institutos y Recursos Humanos

The aim of this project is to determine the transport of nanoparticles (drugs, dendrimers, and others) through the intestine epithelia. There are many proteins in the way of that transport, GAP JUNCTIONS (GJ), TIGHT JUNCTION (TJ), ADHEREN JUNCTIONS (AJ), which work as closed and/or open junctions between neighboring molecules. Open and closed state depend on many factors. Among those factors, there is the Ca+2 concentration. Two Connexons of adjoining Cells form the GJ. The Connexon is formed by six units of CX26 which has been measured by X-ray [1]. Because of that, we choose GJ as the initial junction to study the paracellular transport of nanoparticles through the epithelia. The experimental structure does not show a definitely closed state, and we want to study its behavior on the Ca2+ concentration. In this presentation, we show our preliminary results. We built a model of biological membrane in which the Connexon is embebbed and employed GROMACS code [2] to perform all atom (AA) simulations in order to study the response of the system to different concentrations of Ca2+.Acknowledgments: Financial support of CONICET and University of Buenos Aires is gratefully acknowledged, as the generous allocation of computer resources provided by the Center of High Performance Computing (CHPC) of Utah University.Key words: GAP JUNCTION, CHELATION, TRANSPORT, CONNEXON.References[1] A description of the structural determination procedures of a gap junction channel at 3.5 Å resolution , M. Suga, S. Maeda, S. Nakagawa, E. Yamashita, and T. Tsukihara, Acta Cryst. (2009). D65, 758?766; Gap Junction Hemichannel Interactions with Zwitterionic Lipid, Anionic Lipid, and Cholesterol: Molecular Simulation Studies Andrew Hung and Irene Yarovsky, Biochemistry 2011, 50, 1492?1504.