Abstract
Charge carried by the surface glycocalyx layer (SGL) of the cerebral endothelium has been shown to significantly modulate the permeability of the blood–brain barrier (BBB) to charged solutes in vivo. The cultured monolayer of bEnd3, an immortalized mouse cerebral endothelial cell line, is becoming a popular in vitro BBB model due to its easy growth and maintenance of many BBB characteristics over repeated passages. To test whether the SGL of bEnd3 monolayer carries similar charge as that in the intact BBB and quantify this charge, which can be characterized by the SGL thickness (L f ) and charge density (C mf ), we measured the solute permeability of bEnd3 monolayer to neutral solutes and to solutes with similar size but opposite charges: negatively charged α-lactalbumin (−11) and positively charged ribonuclease (+3). Combining the measured permeability data with a transport model across the cell monolayer, we predicted the L f and the C mf of bEnd3 monolayer, which is ~160 nm and ~25 mEq/L, respectively. We also investigated whether orosomucoid, a plasma glycoprotein modulating the charge of the intact BBB, alters the charge of bEnd3 monolayer. We found that 1 mg/mL orosomucoid would increase SGL charge density of bEnd3 monolayer to ~2-fold of its control value.
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Acknowledgments
This work is supported in part by the National Science Foundation CAREER award, the Andrew Grove Foundation and PSC-CUNY research award of the City University of New York. We also thank Dr. Tao Lowe and Dr. Eun Seok Gil for the QAβCD nanoparticles.
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Associate Editor Julia E. Babensee oversaw the review of this article.
An erratum to this article can be found at http://dx.doi.org/10.1007/s10439-010-0134-z
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Yuan, W., Li, G. & Fu, B.M. Effect of Surface Charge of Immortalized Mouse Cerebral Endothelial Cell Monolayer on Transport of Charged Solutes. Ann Biomed Eng 38, 1463–1472 (2010). https://doi.org/10.1007/s10439-010-9920-x
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DOI: https://doi.org/10.1007/s10439-010-9920-x