Skin barrier formation: The membrane folding model

We propose that skin barrier morphogenesis may take place via a continuous and highly dynamic process of intersection-free membrane unfolding with a c oncomitant crystallization of the emerging multi-lamellar lipid structure r epresenting the developing skin barrier. This implies that the trans-Golgi network and lamellar bodies of the uppermost stratum granulosum cells as we ll as the multilamellar lipid matrix of the intercellular space at the bord er zone between stratum granulosum and stratum corneum could be representat ions of one and the same continuous membrane structure. The profound differ ence between the earlier Landmann model and the membrane folding model pres ented here is that the Landmann model includes changes in membrane topology , whereas topology is kept constant during skin barrier formation according to the membrane folding model. The main advantages of the membrane folding model with respect to the Landmann model are the following: (i) smaller en ergy cost (involves no budding or fusion); (ii) conserves membrane continui ty (preserves water compartmentalization and allows control hereof, membran e continuity essential for barrier function); (iii) allows meticulous contr ol (the thermodynamics of the unfolding procedure are related to curvature energy); (iv) faster (milliseconds, as membrane unfolding basically represe nts a phase transition from cubic-like to lamellar morphology; involves no budding or fusion); (v) membrane folding between lamellar and cubic-like mo rphologies has been identified in numerous biologic systems; (vi) there is experimental evidence for an "extensive intracellular tubulo-reticular cist ernal membrane system within the apical cytosol of the outermost stratum gr anulosum"; and (vii) may explain the reported plethora of forms, numbers, s izes and general appearances of "lamellar bodies" in transmission electron microscopy micrographs.