Transepithelial Electrical Resistance (TEER) is a fundamental measurement used in biology and medicine to quantify the integrity of tissue barriers. These barriers, such as the gut lining or the blood-brain barrier, are cellular structures that separate distinct biological compartments. Their primary function is to create a physical and chemical seal, regulating the movement of ions, solutes, and water. TEER is the standard, non-invasive technique for providing a numerical assessment of how effectively this seal is maintained in a laboratory setting, offering a real-time indicator of a barrier’s health and its ability to restrict the passage of substances.
The Epithelial Barrier: Biological Foundation
Epithelial tissue forms sheets of cells that cover external surfaces and line internal cavities, serving as a selective interface for protection, filtration, and absorption. The integrity of this physical separation is maintained by specialized cell junctions that link neighboring cells together. Tight junctions, also called zonula occludens, govern the paracellular pathway, which is the space between cells. These junctions are intricate networks of proteins, including claudins and occludin, that effectively stitch the plasma membranes of adjacent cells together. By creating this molecular seal, tight junctions force most substances to pass directly through the cell bodies (the transcellular route) rather than slipping between them (the paracellular route). This regulated pathway creates the electrical resistance measured by the TEER method.
Measuring TEER: Methodology and Instrumentation
The quantification of TEER involves applying Ohm’s Law to an epithelial cell layer grown in a laboratory model. Cells are typically cultured on a permeable membrane filter, creating two distinct compartments representing the apical and basolateral sides of a natural barrier. A small, low-frequency alternating electrical current is passed across the monolayer, and the resulting voltage drop is measured.
Specialized instrumentation, often a voltohmmeter, is used with pairs of electrodes. A common configuration utilizes “chopstick” style electrodes, with one placed above the cell layer and the other below it. The electrical resistance of the cell layer is calculated by subtracting the resistance of a blank filter (without cells) from the total resistance measured across the cell-covered filter. To ensure resistance values are comparable across different experiments, the raw electrical resistance, measured in Ohms (\(\Omega\)), is normalized to the surface area of the cell layer. This normalization results in the final standardized unit for TEER: Ohm-centimeters squared (\(\Omega \cdot \text{cm}^2\)).
Interpreting TEER Values and Barrier Function
The numerical value of TEER provides a quantitative measure of barrier function, reflecting how strongly the epithelial layer resists the flow of ions. Higher TEER values indicate a tighter, more restrictive barrier with low permeability. Conversely, a low TEER value signifies a “leaky” or compromised barrier where tight junctions are less sealed, allowing ions and small molecules to pass more freely.
Different tissues exhibit widely varying TEER values depending on their physiological requirements. The blood-brain barrier, which protects the central nervous system, is characterized by very high resistance, sometimes reported as high as 5,900 \(\Omega \cdot \text{cm}^2\). Similarly, the stomach lining is a tight epithelium, exhibiting values near 2,000 \(\Omega/\text{cm}^2\) to prevent acid leakage. In contrast, tissues designed for rapid absorption or secretion, such as the small intestine or certain kidney tubules, have naturally lower resistance. The small intestine, for instance, may show TEER values in the range of 100-180 \(\Omega/\text{cm}^2\).
Applications in Drug Development and Disease Modeling
Measuring Transepithelial Electrical Resistance is a significant technique in pharmacological research and the study of human disease. In drug development, TEER is used extensively to evaluate the permeability of new drug compounds across biological barriers. Scientists use TEER to measure how a potential therapeutic affects barrier integrity or how easily it permeates a model of the target tissue. This is also applied to testing novel drug delivery systems, such as nanoparticles or liposomes, to assess their ability to penetrate a cell layer without causing damage.
In the study of diseases, TEER provides a quantitative marker for conditions where barrier function is compromised. For example, a drop in TEER is often observed in models of inflammatory bowel diseases, such as Crohn’s disease and ulcerative colitis, indicating a loss of intestinal barrier integrity. The measurement helps researchers understand how various pathogens, toxins, or inflammatory signals disrupt the tight junctions. By tracking TEER, investigators can evaluate the effectiveness of new treatments aimed at restoring or enhancing the body’s protective cellular barriers.