The Cornified Cell Envelope: an Important Marker of Stratum Corneum Maturation in Healthy and Dry Skin

The cornified cell envelope (CE) formed by transglutaminase-mediated epsilon-(gamma-glutamyl)lysine cross-linking of specialized corneocyte proteins is the most insoluble component of the terminally differentiated keratinocyte. Under normal Nomarski optics, two types of CE are readily distinguishable: an irregularly shaped, readily deformed 'fragile' envelope (CEf), which predominates in the deepest layers of the stratum corneum, and a polygonal "resilient" or 'rigid' envelope (CEr), which represents over 80% of the CE population in the superficial layers. This distinct spatial distribution indicates a maturation of the CE from the fragile to the resilient morphology during stratum corneum maturation. In this study, we have examined morphological and physical changes occurring in the CE during the terminal differentiation. The proportion of CEf and CEr present in superficial samples of stratum corneum were readily distinguishable following staining with Tetrarhodamine isothiocyanate (TRITC) and showed significant body site variation. The percentage of CEf was highest on samples recovered from exposed body sites (back of hand > cheek > inner arm [bicep region]) suggesting innate body site differences or that photodamage and other environmental trauma can reduce or delay normal CE maturation. Soap-induced dryness resulted in a significant decrease in CE maturation coincidental with reduced corneodesmosomal hydrolysis. Effective moisturization of winter-induced dry skin enhanced CE maturation (33% increase in TRITC fluorescence, n = 14 following 4-week treatment). Using a novel micromanipulation instrument, the force required (microN) to maximally deform individual CEf and CEr was compared. CEf recovered from deep stratum corneum were significantly softer and weaker than CEr recovered from superficial layers. These studies indicate that the normal process of CE maturation is associated with an actual strengthening of this insoluble protective structure and that the impairment of this process is associated with poor quality of the stratum corneum.