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Impedance-based cell monitoring: barrier properties and beyondKeywords: Barrier forming cells, Endothelium, Epithelium, Blood–brain barrier, Electrical resistance, TEER, Impedance spectroscopy Abstract: A characteristic feature of epithelial as well as endothelial cell layers is the formation of intercellular junctions resulting in a tight cellular barrier separating the apical (luminal) from the basolateral (abluminal) side. These cell layers form selectively permeable interfaces between compartments of different chemical composition, thus controlling diffusion along the paracellular way as well as transport processes through intracellular pathways. This is guaranteed by the so-called tight junctions (intercellular connections) that seal the intercellular cleft [1]. An intact barrier is crucial for the physiological activities of the corresponding tissue. However, the barrier is not static but can be modulated by specific stimuli to open and close selectively, thus allowing controlled passage from the blood to the brain or vice versa[2-4]. Developing methods to overcome the barrier is an important issue and highly relevant for medical treatment of diseases within the barriers. Drug delivery systems or strategies to open the barrier temporarily will help to allow medication to cross the blood–brain and the blood-CSF (cerebrospinal fluid) barrier as well as other barriers such as in the intestine, the kidney, the testis and the placenta. Adequate in vitro models are nowadays available, based on cell cultures grown on permeable supports [5]. These are of major importance since the setup offers full access to both the apical and the basolateral compartments. In vitro models can, in principle, be based on primary cells [6,7] or cell lines [8,9]. However, in case of blood–brain barrier (BBB) models most cell lines do not express barrier properties similar to in vivo conditions [10]. Thus care has to be taken if such cells are used for transport experiments.Since the presence of an intact barrier is crucial for reliable in vitro experiments, techniques had to be developed to quantify the barrier integrity. One possibility is to measure the permeability for small hydrophi
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