Skin barrier formation: the membrane folding model

Abstract

We propose that skin barrier morphogenesis may take place via a continuous and highly dynamic process of intersection-free membrane unfolding with a concomitant crystallization of the emerging multilamellar lipid structure representing the developing skin barrier. This implies that the trans-Golgi network and lamellar bodies of the uppermost stratum granulosum cells as well as the multilamellar lipid matrix of the intercellular space at the border zone between stratum granulosum and stratum corneum could be representations of one and the same continuous membrane structure. The profound difference between the earlier Landmann model and the membrane folding model presented 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 energy cost (involves no budding or fusion); (ii) conserves membrane continuity (preserves water compartmentalization and allows control hereof; membrane continuity essential for barrier function); (iii) allows meticulous control (the thermodynamics of the unfolding procedure are related to curvature energy); (iv) faster (milliseconds, as membrane unfolding basically represents a phase transition from cubic-like to lamellar morphology; involves no budding or fusion); (v) membrane folding between lamellar and cubic-like morphologies has been identified in numerous biologic systems; (vi) there is experimental evidence for an “extensive intracellular tubulo-reticular cisternal membrane system within the apical cytosol of the outermost stratum granulosum”; and (vii) may explain the reported plethora of forms, numbers, sizes and general appearances of “lamellar bodies” in transmission electron microscopy micrographs.