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    Area of Science:

    • Cell biology
    • Membrane biophysics

    Background:

    • The structure of the tight junction, a critical component of epithelial cell barriers, remains incompletely understood.
    • Previous analyses of thin-section and freeze-fracture electron microscopy have provided key insights into tight junction morphology.

    Purpose of the Study:

    • To propose a novel structural model for tight-junction strands based on existing observational data.
    • To elucidate the topological and structural basis of tight junction formation and function.

    Main Methods:

    • Analysis of existing thin-section microscopy data.
    • Analysis of existing freeze-fracture electron microscopy data.

    Main Results:

    • Tight junction strands are proposed to be intramembranous, cylindrical, inverted micelles.
    • The exoplasmic halves of plasma membranes fuse into a continuous leaflet at the junctional site.
    • Extracellular spaces are separated by distinct exoplasmic membrane halves and cylindrical micelles.

    Conclusions:

    • The tight junction is structurally and topologically the result of linear fusion between epithelial cell plasma membranes.
    • Junctional stability is maintained by transmembrane proteins interacting with cytoskeletal components, supported by cytoplasmic milieu symmetry.