Transendothelial Electrical ResistanceEdit
Transendothelial Electrical Resistance (TEER) is a widely used, quantitative readout of barrier integrity across endothelial and epithelial cell layers. By measuring the resistance to an applied electrical current across a cell monolayer grown on a porous support, scientists can infer how tightly the cells are joined at their borders and how permeable the layer is to ions and small molecules. TEER is routinely employed in vascular biology, neuroscience, pharmacology, and toxicology to assess the functional state of barriers such as the blood-brain barrier, the intestinal epithelium, and other microvascular or mucosal tissues. It complements biochemical and imaging approaches by providing a rapid, non-destructive, and repeatable metric of barrier health.
The concept rests on the idea that a continuous, intact layer of endothelial or epithelial cells forms a selective barrier with paracellular pathways governed by tight junctions. When tight junctions are robust, ions cannot pass easily between cells, and the electrical resistance across the layer is high. Conversely, disruptions to junctional complexes or cytoskeletal rearrangements that loosen cell–cell contacts reduce resistance and increase paracellular permeability. Because TEER measures the resistance at the macroscopic scale of the cell layer, it captures the cumulative effect of many molecular interactions that regulate barrier function, from tight junction protein expression to cytoskeletal organization and cell viability.
Measurement principles
TEER is typically measured in vitro with cells grown on a porous membrane coated with extracellular matrix components, forming a confluent monolayer on a Transwell insert or similar culture system. An electrode configuration places one pair of electrodes in the apical chamber above the cell layer and another in the basolateral chamber beneath it. The resulting current passes through the paracellular space and the cells themselves, and the measured impedance is converted to resistance. Because the apparent resistance scales with the area of the membrane, researchers normalize the raw resistance to the surface area, yielding a value in ohm·cm^2 (Ω·cm^2). This normalization allows comparisons across experiments and models that use membranes of different sizes.
Two common practical considerations shape TEER measurements:
Temperature and time: TEER is temperature-sensitive and can drift as the culture equilibrates to physiological conditions. Measurements are typically performed at 37°C after the system has stabilized.
Electrode geometry and membrane properties: Electrode placement, insertion design, and the nature of the membrane (e.g., polyester, polycarbonate) influence the absolute impedance. To minimize variability, many laboratories rely on standardized devices such as the Epithelial Volt-Ohm Meter (EVOM) families or equivalent instruments, and report TEER values alongside details of the apparatus and membrane area.
In practice, TEER is frequently interpreted together with permeability assays that use tracer molecules (such as ions, small dyes, or labeled macromolecules). The combination helps distinguish changes in paracellular resistance from alterations affecting transcellular pathways or overall cell health.
Systems and methodologies
The Transwell culture system is the workhorse for TEER measurements in many labs. Endothelial cells, derived from human or animal sources, are seeded onto the porous membrane and given time to form a mature monolayer. The same approach applies to epithelial systems such as intestinal, airway, or renal epithelia. TEER readings can be taken at multiple time points to monitor barrier development, maintenance, and response to stimuli.
In endothelial research, TEER is particularly informative for modeling the vascular barrier that regulates cerebral homeostasis. For brain-related studies, researchers commonly aim to emulate the blood-brain barrier by co-culturing endothelial cells with astrocytes or pericytes and integrating appropriate shear stress, tight junction regulators, and metabolic conditions. The resulting TEER values provide a functional readout of barrier tightness that can be correlated with the expression and localization of tight junction components such as claudin, occludin, and ZO-1.
Beyond Transwells, TEER measurements are adapted to microfluidic systems (often called organ-on-a-chip models) where continuous perfusion, flow-induced shear stress, and three-dimensional architectures better mimic in vivo physiology. In these platforms, TEER remains a key determinant of barrier integrity, though the measurement conventions may differ slightly due to the microenvironment and electrode integration.
Biological determinants of TEER
TEER reflects the cumulative effect of several biological factors that govern barrier function:
Tight junction composition: Proteins such as claudin family members, occludin, and ZO-1 assemble into complexes that regulate paracellular pore size and porosity. Changes in their expression, localization, or phosphorylation state can elevate or reduce TEER.
Cytoskeletal organization: Actin remodeling and associated motor proteins influence cell shape and junctional stability, thereby impacting resistance.
Cell density and viability: Confluent, healthy monolayers yield higher TEER than sparse or dying cells, making TEER a proxy for overall cell health in addition to junctional tightness.
Paracellular pathways: The paracellular route accounts for most ion flux in tight-barrier systems; alterations to this route—whether due to inflammation, oxidative stress, or pharmacologic agents—usually manifest as TEER changes.
External stimuli: Inflammatory cytokines (for example, TNF or IL-1β), mechanical forces, hypoxia, and certain drugs can tighten or loosen junctions, producing measurable shifts in TEER that often precede or accompany changes in molecular permeability.
TEER values vary substantially across cell types. The high TEER typical of brain microvascular endothelium signals a particularly restrictive barrier, whereas other epithelia—such as those in the lung or intestine—may exhibit lower baseline TEER yet remain functionally selective. Accurate interpretation requires model-specific baselines, standardized conditions, and awareness of how experimental variables influence the readout.
Applications and interpretation
TEER is widely used to:
Assess barrier maturation and maintenance in vitro, providing a rapid screen for compounds or genetic modifications that strengthen or weaken junctional integrity.
Evaluate the effect of inflammatory mediators, toxins, pathogens, and therapeutic agents on barrier function, helping to interpret potential side effects or protective strategies.
Support drug development and CNS pharmacology by predicting the ability of molecules to cross tight barriers. While TEER alone cannot quantify permeability to every drug, paired with tracer flux measurements it helps forecast CNS exposure and regional barrier health.
Compare different model systems, such as human versus animal-derived cells, or conventional Transwell setups versus microfluidic organ-on-a-chip platforms, to understand how architecture and flow influence barrier properties.
Within this framework, TEER is often examined alongside molecular readouts, including immunostaining for tight junction proteins, transcript levels of barrier-related genes, and functional assays of transporter activity. Together, these data provide a multi-dimensional view of barrier integrity and function.
In disease and therapy contexts, TEER can help illuminate how the barrier responds to disease drivers or therapeutic interventions. For example, models of the blood-brain barrier are used to study neuroinflammatory processes and to test neuroprotective strategies; intestinal barrier models contribute to understanding inflammatory bowel diseases and nutrient absorption dynamics. See blood-brain barrier and intestinal epithelium for context on tissue-specific applications.
Limitations and debates
Despite its utility, TEER has limitations that researchers must navigate:
Indirect measurement: TEER infers barrier integrity from electrical properties and does not directly measure the flux of every molecule of interest. Permeability to ions can differ from permeability to larger solutes, so TEER should be interpreted with complementary assays.
Membrane and electrode artifacts: Variability stemming from membrane material, coating, pore size, and electrode placement can confound comparisons across laboratories or experiments. Detailed reporting of methods is essential for reproducibility.
Cell-type and condition dependence: Baseline TEER values are model-specific. A higher TEER does not automatically equate to a more physiologic barrier, especially if it arises from non-physiologic conditions or cell stress.
Temporal dynamics: Barrier properties can change over time with culture conditions, mechanical cues, or prolonged exposure to stimuli. Time-matched controls are important for meaningful interpretation.
Standardization challenges: The lack of universal standardization for TEER protocols—such as electrode type, area normalization conventions, and temperature control—can complicate cross-study comparisons. Ongoing efforts aim to harmonize methodologies and reporting practices.
The scientific literature reflects debates about how best to interpret TEER in relation to in vivo barrier function. Some researchers emphasize the need to couple TEER data with quantitative tracer flux measurements and molecular profiling to derive a more complete picture of barrier status. Others argue for standardizing baseline conditions and reporting a comprehensive set of assay parameters to improve reproducibility. Across these discussions, the central point remains: TEER is a powerful, but not solitary, indicator of barrier integrity.
TEER in disease, pharmacology, and modeling
Modeling barrier function with TEER has shed light on pathophysiology and therapeutic strategies. In neurovascular research, TEER helps gauge how disease processes or candidate drugs influence the permeability of the brain vasculature, with implications for treating neurological disorders where barrier dysfunction is a factor. In gastroenterology and pulmonology, TEER-informed models contribute to understanding how inflammatory states alter barrier integrity and how nutritional, microbial, or pharmacologic factors modulate paracellular transport. See blood-brain barrier and gastric mucosa for related barrier contexts.
Beyond basic science, TEER data feed into translational workflows that aim to improve drug delivery and safety assessments. While TEER alone cannot predict clinical outcomes, integrated barrier models support decisions about candidate compounds, dosing strategies, and the prioritization of in vivo studies. This approach aligns with a broader emphasis on mechanistic understanding and cost-effective research design.
The broader literature also considers how TEER measurements can reflect system-level properties such as perfusion, shear stress, and tissue architecture in organoids and microphysiological systems. In these complex models, TEER remains a central, interpretable metric of barrier function amid many interacting variables.