Corneocytes: Relationship between Structural and Biomechanical Properties (original) (raw)
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Understanding age-induced alterations to the biomechanical barrier function of human stratum corneum
Journal of dermatological science, 2015
The appearance and function of human skin are dramatically altered with aging, resulting in higher rates of severe xerosis and other skin complaints. The outermost layer of the epidermis, the stratum corneum (SC), is responsible for the biomechanical barrier function of skin and is also adversely transformed with age. With age the keratin filaments within the corneocytes are prone to crosslinking, the amount of intercellular lipids decreases resulting in fewer lipid bilayers, and the rate of corneocyte turnover decreases. The effect of these structural changes on the mechanical properties of the SC has not been determined. Here we determine how several aspects of the SC's mechanical properties are dramatically degraded with age. We performed a range of biomechanical experiments, including micro-tension, bulge, double cantilever beam, and substrate curvature testing on abdominal stratum corneum from cadaveric female donors ranging in age from 29 to 93 years old. We found that the...
The elastic properties of the stratum corneum have been examined by many investigators, but the morphological evidence for changes in the structure of stratum corneum cohesive elements, lipids and desmosomes, during mechanical extension remains sparse. Additionally, little is known of the effect of mechanical stress on stratum corneum water barrier function. In this study we have examined in detail changes in the structure of the stratum corneum intercellular lipids and desmosomes during linear extension studies on isolated stratum corneum in vitro. Ultrastructural changes have been investigated by electron microscopy, and barrier function has been assessed by measuring water loss through the tissue. Initially, at low extensions of the stratum corneum the structure of the intercellular bilayer lipids appeared normal, during further extension their membrane structure became disrupted, and with continued extension they became progressively disorganized. Desmosomes, by comparison, were more resilient structures, only being perturbed after large extensions during which intercorneocyte desmosomal links were observed to rupture just before the complete fracture of the tissue. These events were associated with increased water loss through the stratum corneum. If these in vitro events are paralleled in vivo, it appears that stratum corneum lipids are sufficiently fluid to maintain barrier function during small extensions of the skin surface. However, following large extensions the structural changes could lead to perturbed water barrier function, desmosome rupture, and aberrant desquamation, resulting in the appearance of xerotic skin conditions. STRATUM CORNEUM LIPIDS 15 !
Implications of normal and disordered remodeling dynamics of corneodesmosomes in stratum corneum
Dermatologica Sinica, 2015
Desmosomes and corneodesmosomes are the most important adhering junctions, providing strength for the epidermal sheet structure made of living keratinocytes and enucleated stratum corneum corneocytes, respectively. These junctions are connected directly with transmembrane desmosomal cadherins, desmogleins (Dsgs), and desmocollins (Dscs); mainly Dsg1/Dsc1 and Dsg3/Dsc3 in desmosomes, and Dsg1/Dsc1 with corneodesmosin in corneodesmosomes. Dsgs and Dscs are associated with several proteins at their inner cytoplasmic domains to anchor keratin intermediate filaments. Desmosomes are not static, but dynamic units that undergo regular remodeling to allow for keratinocyte outwardmigration in the epidermis. In corneodesmosomes, this dynamic nature of desmosomes is lost by fixing desmosomal cadherins with corneodesmosin at the intercellular domain of desmosomes and possibly with the formation of peptide bonds by activation of transglutaminase-1 at the intracellular face of desmosomes. Immediately after formation, corneodesmosomes normally commit to degradation, which is complicatedly regulated by proteolytic cleavage of their respective extracellular portions, via kallikrein-regulated peptidases and cathepsins. This proteolytic activity is in turn controlled by a variety of inhibitory agents, including protease inhibitors, cholesterol sulfate, and an acidic gradient. The impairment of protease control causes keratinization disorders. This review focuses on the regulation of corneodesmosome remodeling in relation to disorders of the stratum corneum.
As the outermost layer of the skin, the stratum corneum participates in the functional properties of the skin (1). For some functions, i.e. photoprotection (2, 3) or barrier protection (4), it is well accepted that the stratum corneum plays the primordial role. Concerning the mechanical properties of the skin, the influence of the mechanical properties of the stratum corneum is also recognized (5,6), but its exact level of importance is still in debates as it doesn’t exist clear results in the literature. The stratum corneum could be considered as a composite material mainly made of corneocytes, intercellular lipids, corneodesmosomes, and other intercellular proteoglycannes. Such a complex material should be characterized in a multi-scale approach in order to relate mechanical properties of the main constituents to macroscopic properties of the skin such as softness, firmness, elasticity, and tonicity. This chapter is divided in three parts as it explores stratum corneum biomechanics at three different scales: the cellular level with descriptions of the corneocyte mechanical properties, the tissue level through mechanical properties obtained on in vitro stratum corneum layer, and finally at the organ level through the description of the contribution of the outermost layer, as a part of a multi-layer organ. Mechanical properties at the different scales will be described on normal stratum corneum, and under variable hydration states, in order to improve our global understanding on water interactions with. Finally, for the three parts, we’ll present a short state-of-the-art review, as well as new results obtained recently in our labs.
Acute Modulations in Permeability Barrier Function Regulate Epidermal Cornification
The American Journal of Pathology, 2008
Stratum corneum comprises corneocytes, derived from outer stratum granulosum during terminal differentiation, embedded in a lipid-enriched extracellular matrix, secreted from epidermal lamellar bodies. Permeability barrier insults stimulate rapid secretion of preformed lamellar bodies from the outer stratum granulosum, regulated through modulations in ionic gradients and serine protease (SP)/protease-activated receptor type 2 (PAR2) signaling. Because corneocytes are also required for barrier function, we hypothesized that corneocyte formation could also be regulated by barrier function. Barrier abrogation by two unrelated methods initiated a wave of cornification, assessed as TdT-mediated dUTP nick end-labeling-positive cells in stratum granulosum and newly cornified cells by electron microscopy. Because cornification was blocked by occlusion, corneocytes formed specifically in response to barrier, rather than injury or cell replacement, requirements. SP inhibitors and hyperacidification (which decreases SP activity) blocked cornification after barrier disruption. Similarly, cornification was delayed in PAR2 ؊/؊ mice. Although classical markers of apoptosis [poly-(ADP-ribose)polymerase and caspase (Casp)-3] remained unchanged, barrier disruption activated Casp-14.
Compartmentalization of the human stratum corneum by persistent tight junction-like structures
Experimental Dermatology, 2011
Several tight junction (TJ) proteins were detected in the living layers of adult human epidermis, and TJ-like membrane ridges were observed at the top of the stratum granulosum (SG) in freeze-fracture studies. We applied standard and immunoelectron microscopy to look for TJ-derived structures in the stratum corneum (SC) of human adult epidermis and in cornified envelopes purified from the plantar SC. Besides confirming claudin-1 labelling in the proximity of SG desmosomes, we also observed immunolocalization near corneodesmosomes in the lower SC. In addition, TJ proteins were consistently detected in the purified cornified envelopes. Lateral but not horizontal walls of the corneocytes showed frequent points of molecular fusion between lipid envelopes. These structural associations were very frequently localized at the top of the lateral corneocyte membranes, thus sealing the extremities of lateral intercorneocyte spaces. We propose that TJ-like structures persist in the SC and contribute to the reinforcement of lateral contacts and to the formation of membrane interdigitations between corneocytes. Their presence could contribute to subdivision of the extracellular spaces of SC into consecutive individualized compartments. Intercellular lipids, enzymes and other (glyco)protein content could thus evolve in the keratinized epidermal layer at different paces, as preprogrammed in the underlying living cells and influenced by the environment, e.g. humidity. Such situation might explain differences in the degradation rates between the 'peripheral' and the 'non-peripheral' corneodesmosomes observed during physiological desquamation, as previously suggested by us and others.
Experimental Cell Research, 1997
During the late stages of epidermal differentiation, protein located in the extracellular part of the modikeratinocytes give rise to ''dead mummified'' cells, i.e., fied desmosomes (corneodesmosomes) of human cornithe corneocytes. Stacking of these cells forms the cornified epithelia, is thought to be a key event of desquafied layer of the epidermis, or stratum corneum (SC), 3 mation. Three monoclonal antibodies specific for huwhich guarantees epidermal permeability barrier and man corneodesmosin were used to search for the is responsible for mechanical protection of the body.
Archives of Dermatological Research, 1994
Corneodesmosin, defined as the protein recognized by the monoclonal antibody G36-19, is a recently described late differentiation protein of human cornified epithelium. In the stratum corneum it is localized in the extracellular parts of modified desmosomes (corneodesmosomes) and adjacent parts of the cornified cell envelope. The aim of the present study was to investigate whether corneodesmosin undergoes changes in the stratum corneum which can be related to the cohesive state of the tissue and to desquamation. Extracts of plantar stratum corneum from various tissue levels and tape-stripped non-palmoplantar stratum corneum were analysed by immunoblotting with G36-19. In addition, the fate of corneodesmosin during shedding of surface cells in a recently described in vitro model of desquamation in plantar stratum corneum was investigated and compared with the degradation of the desmosomal protein desmoglein I in this system. The apparent molecular weights of the major G36-19-positive components in plantar stratum corneum ranged between 33 and 48 kDa. The components with the highest molecular weights were predominant in the deepest tissue layers. In the intermediate tissue layers G36-19-positive components of molecular weight 33-36, 39 and 44-48 kDa were found. There seemed to be a further degradation of the 33 to 36-kDa components in the most superficial parts of the tissue. In surface cells dissociated in vivo as well as in vitro no G36-19-positive components with molecular weights above 36 kDa were detected. Results from analyses of nonpalmoplantar stratum corneum suggested that corneodesmosin is degraded in this tissue in a way that may be similar to that in plantar stratum corneum. In the in vitro system, EDTA caused a marked stimulation of the further degradation of the 33 to 36-kDa G36-19positive components, but appeared not to affect the degradation of desmoglein I. The results are compatible with a role of corneodesmosin in stratum corneum Correspondence to: T. Egelrud cell cohesion. The degradation of this protein may be one of the biochemical changes in the stratum corneum which ultimately leads to desquamation.
Cellular Changes that Accompany Shedding of Human Corneocytes
Journal of Investigative Dermatology, 2012
Corneocyte desquamation has been ascribed to either: 1) proteolytic degradation of corneodesmosomes (CD); 2) disorganization of extracellular lamellar bilayers; and/or 3) 'swellshrinkage-slough' (SSS) from hydration/dehydration. To address the cellular basis for normal exfoliation, we compared changes in lamellar bilayer architecture and CD structure in DSquame® strips from the 1st vs. 5th stripping ('outer' vs. 'mid'-stratum corneum [SC], respectively) from 9 normal adult forearms. Strippings were either processed for standard EM or for ruthenium (Ru-V)-or osmium-tetroxide (Os-V) vapor fixation, followed by immediate epoxy embedment, an artifact-free protocol that to our knowledge is previously unreported. CDs are largely intact in the mid-SC, but replaced by electron-dense (hydrophilic) clefts (lacunae) that expand laterally, splitting lamellar arrays in the outer SC. Some undegraded DSG1/DSC1 redistribute uniformly into corneocyte envelopes (CEs) in the outer SC (shown by proteomics, Z-Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: