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TEER/Barrier Function

Epithelial cells and endothelial cells regulate the passage of molecules across cell layers. Diseases, especially vascular disease, occur when this function is impaired. ECIS® provides a highly sensitive real-time continous TEER measurement ideal for these types of studies.

Monitoring the Barrier Function of Cell Monolayers using ECIS®


In vivo, barriers are provided by monolayers of epithelial or endothelial cells. These cell layers play a key role regulating the free movement of molecules between different tissues and/or interstitial compartments. In many diseases as well as in inflammation, these barriers become compromised, and hence, measuring their permeability is of considerable interest to cell biologists and the health community in general.

Most epithelial and endothelial cells types can be cultured in vitro to form confluent monolayers where it is possible to measure the barrier function afforded by these cell layers. In addition, with the right tools, dynamic changes of the layers can be followed when the cellular environment is altered by exposure to compounds or physical changes such as shear stress.

Barrier Function Measurements

We offer different real-time approaches for electrically monitoring the barrier function (permeability) of cell monolayers using the ECIS® instrumentation. The approach used depends upon the degree of barrier function of the cells being studied, the throughput (number of experimental conditions) required, special experimental conditions (e.g. cells under flow) and, of course, the preference of the researcher. The main consideration, however, is whether one wants to monitor cells grown upon solid substrates or upon membrane filter supports.

  • Monitoring cells upon solid substrates with gold film electrodes is simple and high throughput can easily be achieved (e.g. using 96 well arrays). In addition, this approach allows barrier measurements to be made under shear stress conditions to more closely mimic the in vivo endothelial cell environment.
  • The use of membrane filters as a substrate is experimentally more demanding, however, this approach provides a more in vivo like situation where cells are effectively fed from both the apical and basal side. It is commonly observed that under these conditions cell layers achieve higher absolute barrier function. That being said, the relative change in barrier function observed on both solid and filter supports seem to be comparable.

ECIS Barrier Function Measurements on Gold Film Electrodes

Let's first consider the importance of the AC frequency used in the ECIS constant current measurement. The illustration below shows a cross section of a confluent cells layer where the path of the current is indicated by the arrows. The red arrows represent ion current flow coming from the electrode interface, moving in the solution spaces between the electrode and the basal plasma membrane and then moving through the paracellular passage between the cells (the barrier function). The green arrows on the other hand indicate a path of current that is possible as ECIS is an AC measurement, and current can couple capacitively through the cell membranes.

AC frequency

Current will always follow the path of least resistance. At high AC frequency (40,000 Hz) the impedance (capacitive reactance) of the membrane is relatively small, and current mainly capacitively couples through the insulating cell membranes with little current passing through the paracellular path. At low AC frequency, on the other hand, the membrane impedance is high, and most of the current now flows under the cells and through the tight spaces between the cells (the solution path).

As a result of this difference, high frequency impedance can be used to monitor the establishment of a confluent layer, and low frequency impedance can be used to monitor the solution paths about the cells and hence the layer's barrier function.

Data Taken at Different AC Frequencies with Tight Epithelial Cell Monolayers

The data below report the changes of impedance in two duplicate wells following inoculation of MDCK II cells (canine kidney epithelium). The micrographs show that the cell layer is in place and confluent about 3 hours after inoculation, and this is conveyed by the plateau in the impedance at 40,000 Hz. Measuring the same wells at 400 Hz we see the formation of the barrier function is not completed until about 10 hours after inoculation. This is also confirmed microscopically using stains for the junctional proteins E-cadherin and ZO-1 (zona occludens protein. (Data courtesy of Professor Joachim Wegener, Univ. of Regensburg) For tight epithelial cells, the impedance at low AC frequencies provides a very effective measure of the layer's barrier function.

Cell Coverage

Data from Endothelial Cell Measurements

With endothelial cells, the barrier function is relatively low compared with epithelial cells with tight junctions, and the resistive portion of the ECIS impedance measured at 4000 Hz is commonly used to evaluate barrier function changes. This assay for endothelium was introduced in 1992 (Tiruppathi et.al.) and relied on the use of complex impedance measurements of endothelial cells grown upon ECIS electrodes to report just the resistive portion of the impedance. In this first study, the response of bovine pulmonary microvascular endothelial cells exposed to thrombin was evaluated (see figure below).


Since this first study, the resistive portion of the impedance at 4000 Hz has been used to monitor real-time changes in endothelial permeability in several laboratories, and the assay appears in many peer-reviewed publications. ECIS used in this manner has increasingly become an attractive alternative to Ussing chambers and other membrane filter measurements. In addition to its convenience in gathering barrier function data with a minimum of labor, the measurement also requires no tagged compounds and associated sampling/measuring techniques.

Flow Arrays Measurements

Another important feature of the ECIS system, unlike filter-based assays, is its ability to follow the barrier function of endothelial cell monolayers as they are exposed to flow conditions. This is accomplished using ECIS flow arrays that permit measurements of cell layers subjected to shear stress as high as those experienced in vivo.

Flow Diagram

The ECIS TEER24 Instrument

ECIS TEER24 Literature

We now offer a special single purpose instrument designed to only work with membrane insert filters. The ECIS TEER24 uses a 75 Hz AC frequency to determine TEER value. The measurement consists of three steps; a zero set phase to flat-field the microplate array, setting a reference well to monitor any incubator changes which may occur during the measurement and the data collection phase. The flat-fielding takes into account the resistance of the electrodes in the microplate, solution and filter. During data collection the resistance is measured, and the TEER is calculated by subtracting the flat field zero values and reference well changes and scaling for the surface area of the filter.

Cell Dish

Modeled ECIS Measurements (Pure Paracellular Path Measurements)

When using either the ECIS solid substrate array or measurements with porated filters, there is a component to the solution-path impedance other than the paracellular path - namely the narrow solution passageway sandwiched beneath the cell and its substrate. (Lo et.al.).

In some situations when measuring barrier function (the resistance of the paracellular space), there is another component we refer to as alpha where current also encounters resistance in moving in the narrow spaces between the substrate and the basal plasma membrane.

Constructed Path

This is illustrated in the figure showing a cross section of an epithelial cell with tight junctions to its neighboring cells. In this case, we illustrate a porated filter as the cell substrate, but one could just as well have an ECIS solid substrate beneath the cells. In either situation there is a constricted space beneath the cell (shaded in blue) that must be first traversed before current (or tracers) can pass through the paracellular space (the barrier of interest, shaded in red).

For many epithelial cell layers, the contribution of this passage under the cell is small relative to the tight paracellular passage and does not play a major role in the measurement of barrier function. However, with cells having weaker barrier functions (e.g. some endothelial layers), this may present a complication in making a clean measurement of the paracellular path.

Fortunately, using the ECIS mathematical modeling software (Giaever and Keese), it is possible to separate these two aspects of the measurement. With this feature, time course changes in both the barrier function (Rb) and the passage beneath the cells (alpha) can be independently presented. The modeling software comes standard with the ZTheta instrumentation.

Thrombin Addition

An example is shown of modeled data software, where time course changes of Rb are reported for microvascular endothelial cells exposed to thrombin. The value of alpha remains essentially constant throughout the measurements and is also plotted for comparison.

ECIS Filter Measurements with Tortuous-path Filters

There is another means to eliminate the contribution of the spaces beneath the cells and measure only the paracellular space; this is accomplished using tortuous-path rather than porated filters.

Porated Filter

As shown in the figure, without the vertical pores, current can now flow with little hindrance directly to the cell-cell junctions - essentially eliminating this space (alpha) from the measurement.

Tortuous-path filters for 24 well plates are available from several vendors and can be used with the ECIS TEER24 instrument.

Key References

Tiruppathi, C., Malik, A.B., Del Vecchio, P.J., Keese, C.R., and Giaever,I., Electrical method for detection of endothelial cell shape change in real time, PNAS USA 89, 7919-7923 (1992).

Lo, C.M., Keese, C.R., Giaever, I., "Cell-substrate contact: Another factor may influence transepithelial electrical resistance of cell layers cultured on permeable filters", Experimental Cell Research, 250 (2): 576-580 (1999).

Giaever, I. and Keese,C.R., PNAS USA 88, 7896 (1991).

Related Barrier Function of Cell Layers ECIS Publications

Septin-2 Mediates Airway Epithelial Barrier Function in Physiologic and Pathologic Conditions. VK Sidhaye, E Chau, P Breysse, and LS King. Am J Respir Cell Mol Biol. 2010.

Epidermal growth factor receptor signaling contributes to house dust mite-induced epithelial barrier dysfunction. I.H. Heijink, A. van Oosterhout, and A. Kapus
Eur. Respir. J. 2010; 36:1016-1026.

Effect of a novel multipurpose contact lens solution on human corneal epithelial barrier function. ME Cavet, KR Vandermeid, KL Harrington, R Tchao, KW Ward, and JZ Zhang. Cont Lens Anterior Eye. 2010.

The PI3K p110α isoform regulates endothelial adherens junctions via Pyk2 and Rac1. RJ Cain, B Vanhaesebroeck, and AJ Ridley. J Cell Biol. 2010; vol:188 iss:6 pg:863 -876

EGFR signaling contributes to house dust mite-induced epithelial barrier dysfunction. I.H. Heijink, A. van Oosterhout, and A. Kapus. Eur. Respir. J. published 29 March 2010, 10.1183/09031936.00125809.

Desmoglein 2-mediated adhesion is required for intestinal epithelial barrier integrity. Nicolas Schlegel, Michael Meir, Wolfgang-Moritz Heupel, Bastian Holthöfer, Rudolf E. Leube, and Jens Waschke. Am J Physiol Gastrointest Liver Physiol. 2010; 298:G774-G783.

Calcium/calmodulin-dependent protein kinase II delta6 (CaMKIIdelta6) and RhoA involvement in thrombin-induced endothelial barrier dysfunction. Zhen Wang, Roman Ginnan, Iskandar F. Abdullaev, Mohamed Trebak, Peter A. Vincent, and Harold A. Singer. J. Biol. Chem. published 4 May 2010, 10.1074/jbc.M110.120790.

Group V Phospholipase A2 Mediates Barrier Disruption of Human Pulmonary Endothelial Cells Caused by LPS in Vitro. Steven M. Dudek, Nilda M. Muñoz, Anjali Desai, Christopher M. Osan, Angelo Y. Meliton, and Alan R. Leff. Am. J. Respir. Cell Mol. Biol. published 6 May 2010, 10.1165/rcmb.2009-0446OC.

Adenosine protected against pulmonary edema through transporter- and receptor A2-mediated endothelial barrier enhancement. Qing Lu, Elizabeth O. Harrington, Julie Newton, Brian Casserly, Gregory Radin, Rod Warburton, Yang Zhou, Michael R. Blackburn, and Sharon Rounds. Am J Physiol Lung Cell Mol Physiol. 2010; 298:L755-L767.

Regulation of CovR expression in Group B streptococcus impacts blood-brain barrier penetration. A Lembo, MA Gurney, K Burnside, A Banerjee, M de Los Reyes, JE Connelly, WJ Lin, KA Jewell, A Vo, CW Renken, KS Doran, and L Rajagopal. Mol Microbiol. 2010.

Cellular mechanisms of IL-17-induced blood-brain barrier disruption. Jula Huppert, Dorothea Closhen, Andrew Croxford, Robin White, Paulina Kulig, Eweline Pietrowski, Ingo Bechmann, Burkhard Becher, Heiko J. Luhmann, Ari Waisman, and Christoph R. W. Kuhlmann. FASEB J. 2010 Apr;24(4):1023-34. Epub 2009 Nov 25.

Kei Sarai, Kenichi Shikata, Yasushi Shikata, Kazuyoshi Omori, Naomi Watanabe, Motofumi Sasaki, Shingo Nishishita, Jun Wada, Noriko Goda, Noriyuki Kataoka, and Hirofumi Makino. Endothelial barrier protection by FTY720 under hyperglycemic condition: involvement of focal adhesion kinase, small GTPases, and adherens junction proteins. Am J Physiol Cell Physiol. 2009; 297:C945-C954.

Jula Huppert, Dorothea Closhen, Andrew Croxford, Robin White, Paulina Kulig, Eweline Pietrowski, Ingo Bechmann, Burkhard Becher, Heiko J. Luhmann, Ari Waisman, and Christoph R. W. Kuhlmann. Cellular mechanisms of IL-17-induced blood-brain barrier disruption. FASEB J. published 25 November 2009, 10.1096/fj.09-141978.

Donghong He, Yanlin Su, Peter V. Usatyuk, Ernst Wm. Spannhake, Paul Kogut, Julian Solway, Viswanathan Natarajan, and Yutong Zhao, Lysophosphatidic Acid Enhances Pulmonary Epithelial Barrier Integrity and Protects Endotoxin-induced Epithelial Barrier Disruption and Lung Injury. The Journal of Biological Chemistry, Vol. 284, NO. 36, pp. 24123–24132, September 4, 2009.

Tripathi, A. K., Sullivan, D.J., Stins, M.F., Plasmodium falciparum-Infected Erthyrocytes Decrease the Integrity of Human Blood-Brain Barrier Endothelial Cell Monolayers, J. of Infectious Diseases: 942-950 (2007).

Litkouhi, B., Kwong, J., Lo, C.M., Smedley, J.G., McClane, B.A, Aponte, M., Gao, Z., Sarno, J.L., Hinners, J., Welch, W.R., Berkowitz, R.S., Mok, S.C., Garner, E.I.O., Claudin-4 Overexpression in Epithelial Ovarian Cancer Is Associated with Hypomethylation and Is a Potential Target for Modulation of Tight Junction Barrier Function Using a C-Terminal Fragment of Clostridium perfringens Enterotoxin. Neoplasia: 304-314 (2007).

Hartmann, C., Zozulya, A., Wegener, J., Galla, H.J., The impact of glia-derived extracellular matrices on the barrier function of cerebral endothelial cells: An in vitro study, Experimental Cell Research (2007).

Chiang, E.T., Persaud-Sawin, D.A., Kulkarni, S., Garcia, J.G., Imani, F., Bluetongue Virus and Double-Stranded RNA Increase Human Vascular Permeability: Role of p38 MAPK, J Clin Immunol. [Epub ahead of print] (2006).

Yin F, Watsky MA. LPA and S1P Increase Corneal Epithelial and Endothelial Cell Transcellular Resistance, Invest Ophthalmol Vis Sci. 46(6):1927-33 (2005).

Weidenfeller, C., Schrot, S., Zozulya, A., Galla, H.J., Murine brain capillary endothelial cells exhibit improved barrier properties under the influence of hydrocortisone, Brain Res. 1053(1-2):162-74 (2005).

McLaughlin, J.N., Shen, L., Holinstat, M., Brooks, J.D., DiBenedetto, E., Hamm, H.E., Functional Selectivity of G Protein Signaling by Agonist Peptides and Thrombin for the Protease-activated Receptor-1. J. Biol. Chem. 280(26): 25048-25059 (2005).

McLaughlin, J.N., Mazzoni, M.R., Cleator, J.H., Earls, L., Perdigoto, A.L., Brooks, J.D., Muldowney, J.A.S., Vaughan, D.E., Hamm, H.E. , Thrombin Modulates the Expression of a Set of Genes Including Thrombospondin-1 in Human Microvascular Endothelial Cells, J. Biol. Chem. 280(23): 22172-22180 (2005).

Wu, M.H., Endothelial focal adhesions and barrier function, J. Physiology. 569(2): 359 (2005).

Treeratanapiboon, L., Psathaki, K., Wegener, J., Looareesuwan, S., Galla, H.J., Udomsangpetch, R. In vitro study of malaria parasite induced disruption of blood-brain barrier, Biochem Biophys Res Commun. 335(3):810-8 (2005).

Aigul Moldobaeva, Laura E Welsh-Servinsky, Larissa A Shimoda, R. Scott Stephens, Alexander D Verin, Rubin M Tuder, and David B Pearse Role of Protein Kinase G in Barrier Protective Effects of cGMP in Human Pulmonary Artery Endothelial Cells, Am J Physiol Lung Cell Mol Physiol, 0: 4342005 (2005).

Anna A Birukova, Djanybek Adyshev, Boris Gorshkov, Gary M Bokoch, Konstantin G Birukov, and Alexander A Verin GED-H1 is Involved in Agonist-induced Human Pulmonary Entotherlial Barrier Dysfunction, Am J Physiol Lung Cell Mol Physiol, 0: 2592005 (2005).

Grab, D.J., Nikolskaia, O., Kim, Y.V., Lonsdale-Eccles, J.D., Ito, S., Hara, T., Fukuma, T., Nyarko, E., Kim, K.J., Stins, M.F., Delannoy, M.J., Rodgers, J., Kim, K.S., African Trypanosome Interactions With an In Vitro Model of the Human Blood-Brain Barrier, J Parasitology, 90(5): 970-979 (2004).

Birukova, A.A., Birukov, K.G., Smurova, K., Adyshev, D., Kaibuchi, K., Alieva, I., Garcia, J.G.N., Verin, A.D., Novel role of microtubules in thrombin-induced endothelial barrier dysfunction, The FASEB Journal. 18:1879-1890, (2004).

Jacobson, J.R., Dudek, S.M., Birukov, K.G., Ye, S.Q., Grigoryev,D.N., Girgis, R.E., Garcia, J.G.N. Cytoskeletal Activation and Altered Gene Expression in Endothelial Barrier Regulation by Simvastatin, American Journal of Respiratory Cell and Molecular Biology. Vol. 30, pp. 662-670, (2004).

Zeng, W., Matter, W.F., Yan, S.B., Um, S.L., Vlahos, C.J., Liu, L., Effect of drotrecogin alfa (activated) on human endothelial cell permeability and Rho kinase signaling, Critical Care Medicine. 32(5): S302-S308 (2004).

Regard, J.B., Scheek, S., Borbiev, T., Lanahan, A.A., Schneider, A., Demetriades, A.M., Hiemisch, H., Barnes, C.A., Verin, A.D., Worley, P.F. , Verge: A Novel Vascular Early Reponse Gene, The Journal of Neuroscience. 24(16):4092-4103 (2004)

Kilani, M.M., Mohammed, K.A., Nasreen, N., Hardwick, J.A., Kaplan, M.H., Tepper, R.S., Antony, V.B. Respiratory syncytial virus causes increased bronchial epithelial permeability, Chest 126(1):186-91 (2004)

Tsikitis, V., Morin, N., Harrington, E., Albina, J., Reichner, J. The Lectin-Like Domain of Comple,emt Receptor 3 Protects Endotherlial Barrier Function from Activated Neutrophils, The Journal of Immunology 173: 1284-1291 (2004).

Iyer, S., Ferreri, D.M., DeCocco, N.C., Minnear, F.L., Vincent, P.A. VE-cadherin-p120 interaction is required for maintenance of endothelial barrier function, Am J Physiol Lung Cell Mol Physiol. 286(6):L1143-53. (2004)

Pearse, P.M., Shimoda, L.A., Verin, A.D., Bogatcheva, N., Moon, C., Ronnett., G.V., Welsh, L.A., Becker, P.M., Effect of cGMP on hydrogen peroxide- induced barrier dysfunction in lung microvascular endothelium, Endothelium, 10:309-317, (2003).

Tar, K., Birukova, A.A., Csortos, C., Bakó, E., Garcia, J.G.N., Verin, A.D., Phosphatase 2A is involved in endothelial cell microtubule remodeling and barrier regulation, Journal of Cellular Biochemistry Vol 92, Issue 3 , 534 - 546, (2003).

Schaphorst, K.L., Chiang, E., Jacobs, K.N., Zaiman, A., Natarajan, V., Wigley, F., Garcia, J.G.N., Role of sphingosine-1 phosphate in the enhancement of endothelial barrier integrity by platelet-released products, Am J Physiol Lung Cell Mol Physiol 285: L258-L267, (2003).

Usatyuk, P.V., Fomin, V.P., Shi, S., Garcia, J.G.N., Schaphorst, K., Natarajan, V., Role of Ca2+ in diperoxovanadate-induced cytoskeletal remodeling and endothelial cell barrier function, Am J Physiol Lung Cell Mol Physiol 285: L1006-L1017, (2003).

Lum, Hazel, Qiao, Jing, Walter, Robert J., Huang, Fei, Subbaiah, Papasani V., Kim, Kwang S., and Holian, Oksana. Inflammatory Stress Increases Receptor for Lysophosphatidylcholine in Human Microvasucal Endothelial Cells, Amer. J. Physiol., in press, (2003).

Birukov, K.G., Jacobson, J.R., Flores, A.A., Ye, S.Q., Birukova, A.A., Verin, A.D., Garcia, J.G.N. , Magnitude-dependent regulation of pulmonary endothelial call barrier function by cyclic stretch, Am J Physiol Lung Cell Mol Physiol. 285: L785-L797 (2003).

van Wetering, S., van den Berk, N., van Buul, J.D., Mul, F.P.J., Lommerse, I., Mous, R., ten Klooster, J.P., Zwaginga, J.J,. Hordijk, P.L. , VCAM-1-mediated Rac signaling controls endothelial cell-cell contacts and leukocyte transmigration, American Journal of Physiology-Cell Physiology, 285 (2): C343-C352 (2003).

Qiao, Jing, Huang, Fei , and Lum, Hazel. PKA Inhibits RhoA Activation: A Protection Mechanism Against Endothelial Barrier Dysfunation, Amer. J. Physiol, 284: L972-L980, (2003).

Tiruppathi, C., Freichel, M., Vogel, S.M., Paria, B.C., Mehta, D., Flockerzi, V., Malik, A.B. Impairment of Store-Operated Ca ^ 2+ Entry in TRPC4 ^ -/- Mice Interferes With Increase in Lung Microvascular Permeability, Circulation Research 91: 70-76 (2002).

Goldberg PL, MacNaughton DE, Clements RT, Minnear FL, Vincent PA. p38 MAPK activation by TGF-beta1 increases MLC phosphorylation and endothelial monolayer permeability, Am J Physiol Lung Cell Mol Physiol. 282(1):L146-54. PMID,(2002).

Kataoka, N., Iwaki, K., Hashimoto, K., Mochizuki, S., Ogasawara, Y., Sato, M., Tsujioka, K., Kajiya, F., Measurements of endothelial cell-to-cell and cell-to-substrate gaps and micromechanical properties of endothelial cells during monocyte adhesion, The National Academy of Sciences of the United States of America, 99 (24): 15638-15643 (2002).

Antony, A.B., Tepper, R.S., Mohammed, K.A., Cockroach extract antigen increases bronchial airway epithelial permeability, Journal of Allergy and Clinical Immunology, 110 (4): 589-595 (2002).

Lum, Hazel, Hao, Zengping, Gayle, Dave, Kumar, Priyadarsini, Patterson, Carolyn E., and Uhler, Michael D. . Vascular Endothelial Cells Express Isoforms of Protein Kinase A Inhibitor, Amer J. Physiol., 282: C59-C66, (2002).

Garcia, J.G.N., Liu, F., Verin, A.D., Birukova, A., Dechert, M.A., Gerthoffer, W.T., Bamberg, J.R., English, D., Sphingosine 1-phosphate promotes endothelial cell barrier integrity by Edg-dependent cytoskeletal rearrangement, J Clin Invest. 108(5): 689?701, (2001).

Minnear FL, Patil S, Bell D, Gainor JP, Morton CA. Platelet lipid(s) bound to albumin increases endothelial electrical resistance: mimicked by LPA, Am J Physiol Lung Cell Mol Physiol. 281(6):L1337-44. PMID, (2001).

Gainor JP, Morton CA, Roberts JT, Vincent PA, Minnear FL. Platelet-conditioned medium increases endothelial electrical resistance independently of cAMP/PKA and cGMP/PKG, Am J Physiol Heart Circ Physiol. Nov;281(5):H1992-2001. PMID (2001).

Becker, Patrice M. , Verin, Alexander D., Booth, Mary Ann, Liu,Feng, Birukova, Anna and Garcia, Joe G. N., Differential regulation of diverse physiological responses to VEGF in pulmonary endothelial cells, Amer J. Physiol., 281: L1500-L1511, (2001).

Hillebrandt, H. Abdelghani,A. Abdelghani-Jacquin,C. Aepfelbacher,M. Sackmann, ., Electrical and optical characterization of thrombin-induced permeability of cultured endothelial cell monolayers on semiconductor electrode arrays, Applied Physics A-Material Science & Processing, 73 (5): 539-546 (2001).

Lum, Hazel, Podolski, J.L., Gurnack, K.L., Schulz, I.T., Huang, F. and Holian, O. Protein Phosphatase 2B Inhibitor Potentiates PKC Activity and Endothelial Barrier Dysfunction, Amer. J. Physiol., 281: L546-555, (2001).

Sandoval, R., A. B. Malik., T. Naqvi, D. Metha, and C. Tiruppathi. Requirement for Ca2+ signaling in the mechanism of thrombin-induced increase in endothelial permeability, Am. J. Physiol. 280:L239-L247, (2001).

Sandoval, R., A. B. Malik., R. D. Minshall, P. Kouklis, C. A. Ellis, and C. Tiruppathi. Ca 2+ signaling and PKC? activate increased endothelial permeability by disassembly of VE-cadherin junctions, J. Physiol. (London).533:433-445, (2001).

Sandoval, R., A. B. Malik., R. D. Minshall, P. Kouklis, C. A. Ellis, and C. Tiruppathi. Ca 2+ signaling and PKC? activate increased endothelial permeability by disassembly of VE-cadherin junctions, J. Physiol. (London).533:433-445, (2001).

Minnear FL. Patil S, Bell D, Gainor JP, Morton CA. Related Articles Platelet lipid(s) bound to albumin increases endothelial electrical resistance: mimicked by LPA, Am J Physiol Lung Cell Mol Physiol. 281(6):L1337-44, (2001).

Ellen, R.P., Ko, K.S.S., Lo, C.M., Grove, D.A., Ishihara, K. Insertional Inactivation of the prtP Gene of Treponema denticola Confirms Dentilisin's Disruption of Epithelial Junctions, J. Mol. Microbiol. Biotechnol. 2(4): 581-586, (2000).

Tsukahara, H., Noiri, E., Jiang, M.Z., Hiraoka, M., Mayumi, M. Role of nitric oxide in human pulmonary microvascular endothelial cell adhesion, Life Sci. 67(1):1-11 (2000).

Ellen, R.P., Ko, K.S., Lo, C.M., Grove, D.A., Ishihara, K. Insertional inactivation of the prtP gene of Treponema denticola confirms dentilisin's disruption of epithelial junctions, J Mol Microbiol Biotechnol. 2(4):581-6 (2000).

Patterson, C.E., Lum, H. Schaphorst, K.L., Verin, A.D., and Garcia, J.G.N. Regualtion of Endothelial Barrier Function by the cAMP-dependent Protein Kinase, Endotherlium, 7(4): 287-308, 2000

Waypa GB, Morton CA, Vincent PA, Mahoney JR Jr, Johnston WK III, and Minnear FL. Oxidant-increases endothelial permeability: prevention with phosphodiesterase inhibition vs cAMP production, J Appl Physiol 88:835-842, 2000.

Lo, C.M., Keese, C.R., Giaever, I. , Cell-substrate contact: Another factor may influence transepithelial electrical resistance of cell layers cultured on permeable filters, Experimental Cell Research, 250 (2): 576-580 (1999).

Ellis, C. A., C. Tiruppathi, R. Sandoval, W.D. Niles, and Malik. A. B. Time course of recovery of endothelial cell surface thrombin receptor (PAR-1) expression, Am. J. Physiol. 276:C38-C45, 1999.

Moy, A.B., Winter, M., Kamath, A., Blackwell, K., Reyes, G., Giaever, I., Keese, C., Shasby, D.M., Histamine alters endothelial barrier function at cell-cell and cell-matrix sites, American Journal of Physiology-Lung Cellular and Molecular Physiology, 278 (5): L888-L898 (2000).

Patil S, Kaplan JE, Minnear FL. Protein, not adenosine or adenine nucleotides, mediates platelet decrease in endothelial permeability, Am J Physiol. Nov; 273(5 Pt 2):H2304-11. PMID (1997)

Tiruppathi, C., W. Song., M. Bergenfeldt. P. Sass and A.B. Malik. Gp60 activation mediates albumin transcytosis in endothelial cells bytyrosine kinase-dependent pathway, J. Biol. Chem. 272:25968-25975,

Tiruppathi, C., Malik, A.B., Del Vecchio, P.J., Keese, C.R., and Giaever,I., Electrical method for detection of endothelial cell shape change in real time, PNAS USA 89, 7919-7923 (1992).

Example Publication

Kim et al., (2015) "Critical Role of Sphingosine-1-Phosphate Receptor-2 in the Disruption of Cerebrovascular Integrity in Experimental Stroke." Nature Communications 6:7893 doi:10.1038/ncomms8893