Epithelial geometry and its physiological properties:revision of the osmotic flow water transport model with LI-cadherin assisting role.
Sprache des Vortragstitels:
We introduce a mathematical model of an absorbing leaky epithelium to reconsider the problem established by
Diamond and Bossert in 1967 of whether ?[?] some distinctive physiological properties of epithelia might arise as
geometrical consequences of epithelial ultrastructure?. We derive analytical expressions for a homogeneous
concentration and for the spatial scale necessary for homogeneity to develop along the cleft. We found that a columnar
epithelium is generally more stable to lumen hyperosmolarity than a cuboidal one. Nevertheless, the cuboidal
epithelium can perform ?uphill? water transport both by narrowing of the intercellular cleft (IC) width and by varying
the expression level of aquaporins and ion channels in an enterocyte. Narrowing of the cleft increases ion concentration
dramatically and can therefore prevent any outflow through tight junctions (TJs) and the lateral membrane as long as a
certain extremely high threshold lumen osmolarity is not reached. Our model predicts that the system is to some extent
self-regulating and thereby prevents fluxes into the lumen. Several theoretical scenarios of water fluxes through TJs,
lateral membrane and opening of the cleft suggest an ability of enterocytes to adjust their parameters to changing
lumen osmolarity. Analytical approximations for IC ion concentrations in columnar and cuboidal epithelia are derived.
Recent experimental evidence has shown that liver-intestine (LI) cadherin can control the up/down flux in intestines
via regulation of the cleft width. This finding is in full agreement with our theoretical model. We suggest that LIcadherin
may increase water transport through epithelia via sequential narrowing of the cleft, starting from the highest
concentration area at the beginning of the cleft and triggering a propagating squeezing motion.