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Am J Physiol Cell Physiol 289: C735-C747, 2005. First published May 4, 2005; doi:10.1152/ajpcell.00103.2005
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METHODS IN CELL PHYSIOLOGY

Modeling error and stability of endothelial cytoskeletal membrane parameters based on modeling transendothelial impedance as resistor and capacitor in series

James E. Bodmer,1,3 Anthony English,4 Megan Brady,3 Ken Blackwell,3 Kari Haxhinasto,3 Sunaina Fotedar,2,3 Kurt Borgman,3 Er-Wei Bai,1,* and Alan B. Moy2,3,*

1Department of Electrical and Computer Engineering and 2Department of Biomedical Engineering, University of Iowa College of Engineering; 3Department of Internal Medicine, University of Iowa College of Medicine and Veterans Administration Hospital, Iowa City, Iowa; and 4Department of Aeronautical, Mechanical and Biomedical Engineering, University of Tennessee, Knoxville, Tennessee

Submitted 7 March 2005 ; accepted in final form 2 May 2005

Transendothelial impedance across an endothelial monolayer grown on a microelectrode has previously been modeled as a repeating pattern of disks in which the electrical circuit consists of a resistor and capacitor in series. Although this numerical model breaks down barrier function into measurements of cell-cell adhesion, cell-matrix adhesion, and membrane capacitance, such solution parameters can be inaccurate without understanding model stability and error. In this study, we have evaluated modeling stability and error by using a {chi}2 evaluation and Levenberg-Marquardt nonlinear least-squares (LM-NLS) method of the real and/or imaginary data in which the experimental measurement is compared with the calculated measurement derived by the model. Modeling stability and error were dependent on current frequency and the type of experimental data modeled. Solution parameters of cell-matrix adhesion were most susceptible to modeling instability. Furthermore, the LM-NLS method displayed frequency-dependent instability of the solution parameters, regardless of whether the real or imaginary data were analyzed. However, the LM-NLS method identified stable and reproducible solution parameters between all types of experimental data when a defined frequency spectrum of the entire data set was selected on the basis of a criterion of minimizing error. The frequency bandwidth that produced stable solution parameters varied greatly among different data types. Thus a numerical model based on characterizing transendothelial impedance as a resistor and capacitor in series and as a repeating pattern of disks is not sufficient to characterize the entire frequency spectrum of experimental transendothelial impedance.

cell-cell adhesion; cell-matrix adhesion; cell membrane capacitance; mathematical computation



Address for reprint requests and other correspondence: A. B. Moy, Dept. of Internal Medicine, C33 GH, Univ. of Iowa College of Medicine, 200 Hawkins Drive, Iowa City, IA 52242 (e-mail: alan-moy{at}uiowa.edu)




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