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Late News: Monitoring Reversible Tight Junction Modulation with a Current-Driven Organic Electrochemical Transistor
Katharina Lieberth1,Maximilian Brückner1,2,Fabrizio Torricelli3,Volker Mailänder1,2,Paschalis Gkoupidenis1,Paul Blom1
Max-Planck Institute for Polymer Research1,University Medical Center of the Johannes Gutenberg-University Mainz2,University of Brescia3
Present characterization techniques for the tight junction modulation are either invasive, such as fluorescence marking, or have low ion sensitivity, like trans-epithelial electrical resistance. The organic electrochemical transistor (OECT) is able to operate in aqueous solutions at low voltages, so it is a biocompatible, label-free and low-cost ion-to-electron converter. Therefore, OECTs are suited biosensors for drug delivery and related processes as cell barrier integrity. The passage of nutrients and drugs into the blood is regulated by the barrier functionality of a cell layer. Hence, modulating the barrier functionality by external chemical agents like poly-L-lysine (PLL) is crucial for drug delivery. The ability of a cell layer to impede the passage of ions through it and therefore to act as a barrier, can be assessed electrically by measuring the resistance across the cell layer. Here, we used an OECT in a current-driven configuration for the evaluation of reversible modulation of tight junctions in the epithelial colon carcinoma (Caco-2) cell line, found in the small intestine, over time. Operating the OECT in current-driven configuration enhances the sensitivity, required to study reversible ion permeability through tight junctions of Caco-2 cells. The reversible opening and closing of tight junctions was detected using the PLL at RT and under physiological conditions. Concentration and time dependent experiments resumed that the exposure to low and medium concentrations of PLL initiates reversible modulation, whereas a too high concentration induces an irreversible barrier disruption due to non-functional tight junction proteins. To support electrical measurements occluding-staining has been performed using immunofluorescence imaging. The results demonstrate the suitability of OECTs to in-situ monitor temporal barrier modulation and recovery, which can offer valuable information for drug delivery applications.
 M. Ramuz, A. Hama, M. Huerta, J. Rivnay, P. Leleux, R. M. Owens, Adv. Mater. 2014, 7083.
 L. H. Jimison, S. A. Tria, D. Khodagholy, Gurfinkel M., E. Lanzarini, A. Hama, G. G. Malliaras, R. M. Owens, Adv. Mater. 2012, 5919.
 J. Rivnay, P. Leleux, M. Sessolo, D. Khodagholy, T. Hervé, M. Fiocchi, G. G. Malliaras, Advanced materials (Deerfield Beach, Fla.) 2013, 25, 7010.
 N. Y. Shim, D. A. Bernards, D. J. Macaya, J. A. DeFranco, M. Nikolou, R. M. Owens, G. G. Malliaras, Sensors 2009, 9896.
 G.T.A. McEwan, M. A. Jepson, B. H. Hirst, N. L. Simmons, Biochemica et Biophysica Acta 1993, 1148, 51.
 M. S. Balda, K. Matter, Seminars in cell & developmental biology 2000, 11, 281.
 a) M. Ghittorelli, L. Lingstedt, P. Romele, N. I. Crăciun, Z.M. Kovács-Vajna, P.W.M. Blom, F. Torricelli, Nature Communications 2018, 1441; b) L. V. Lingstedt, M. Ghittorelli, M. Brückner, J. Reinholz, N. I. Crăciun, F. Torricelli, V. Mailänder, P. Gkoupidenis, P. W. M. Blom, Advanced healthcare materials 2019, 8, e1900128.