Barrier Forming Tissue
In multicellular organisms epithelial and endothelial cell layers serve
as functional barriers and perform very complex and vital activities.
While comprising various tissues of the body, these cell layers form
selectively permeable interfaces between compartments of different
chemical composition. They not only control diffusive permeation of
solutes along intercellular clefts between adjacent cells but can also
actively transport substances along transcellular paths. Key components
of epithelial and endothelial cell barriers are the connecting points
between adjacent cells. These tight junctions are of particular
relevance for the active barrier functionality of the cell layer. They
regulate the passage of molecules across the barrier as they
selectively open and close in response to various signals from the
inside and outside of the cells.
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Epithelial and endothelial cell layers form selectively permeable
barriers. Transport of molecules and ions from the apical to the
basolateral side and vice versa requires passage either through the
cells (transcellular route) or between the cells and thus through tight
junctions (paracellular route). |
While the barrier function is responsible for a multitude of
physiological activities and is thereby of vital importance for the
correct functioning of the organism, it is at the same time also a
severe obstacle for specific types of medical treatment, in particular
for targeted drug delivery: in order to get a drug to the intended site
of action it has somehow to pass through these tissue barriers.
Consequently, in the field of fundamental research, pharmaceutical
research, and drug development there is great interest in understanding
and controlling the barrier function of epithelial and endothelial
tissue. Finding methods to overcome this hurdle is of particular
relevance to medication by drug delivery across the blood-brain
barrier, blood vessels, nasal tissue, or gastrointestinal tissue.
Therefore adequate in vitro cell models and assays are required - for
instance for identifying compounds that reversibly increase drug
permeation through tissue barriers.
A direct correlation between the permeability of a cell layer and its
electric resistance, i.e. the so called transepithelial / -endothelial
electric resistance TER, exists. This fact can be utilized to form the
basis for an assay: tight cell layers exhibit high electric resistance
and - vice versa - high permeability correlates with low electric
resistance. Therefore, the electric resistance measured across a cell
layer is a highly qualified parameter for quantifying leak tightness of
barrier forming tissue. Consequently, it can be recorded to compare and
monitor the establishment or modulation of barrier-forming cell-to-cell
contacts.
Analyzing the properties of a cell layer by means of electrical
measurements is not limited to measuring the electric resistance, but
can be complemented by recording the electric capacitance Ccl as well.
This parameter provides additional information about the cell layer properties:
in particular it is indicative of the expression of microvilli and other membrane extrusions.
The two quantities, resistance TER and capacitance Ccl,
combine for the complex impedance Z of the cell layer, which can be
measured electronically. In contrast to other assay techniques
electrical measurements require neither a fluorescent or radioactive
marker nor any other type of physiologic modification of the cell
system. While providing a wealth of information on the barrier
properties electrical measurements can be performed without affecting
the native cell culture under investigation.