CHAPTER 3 Biophysical Methods to Study Tight Junction Permeability Dorothee Gu ¨nzel, Susanne M. Krug, Rita Rosenthal, and Michael Fromm Institute of Clinical Physiology, Campus Benjamin Franklin, Charite ´, Berlin, Germany I. Overview II. Introduction III. Resistance Measurements A. Transepithelial Resistance (TER, R t ) B. Chopstick Electrodes C. Ussing Chamber D. Impedance Spectroscopy E. One-Path Impedance Spectroscopy F. Two-Path Impedance Spectroscopy G. Conductance Scanning IV. Ion Permeability Measurements A. Ion Flux Measurements B. Dilution and Biionic Potentials C. Conductance Measurements V. Fluxes of Uncharged Paracellular Tracers VI. Paracellular Water Transport VII. Experimental Strategies for TJ Perturbation A. Cell Culture Models: Overexpression and Knockdown B. In Vivo Models: Knockout Mice C. Established Mouse Models VIII. Conclusion References Current Topics in Membranes, Volume 65 1063-5823/10 $35.00 Copyright 2010, Elsevier Inc. All right reserved. DOI: 10.1016/S1063-5823(10)65003-X