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Title: Modelling the depth-dependent permeability barrier of the skin
Author: van Logtestijn, Mark Daniel
ISNI:       0000 0004 8499 3686
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2017
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In the upper layers of our skin, the stratum corneum and the tight junctions in the stratum granulosum form permeability barriers which prevent dehydration and protect against external pathogens. The onset and deterioration of skin diseases, such as atopic dermatitis, are often caused or accompanied by barrier defects due to dysregulation of barrier homeostasis. As the cells constantly move up through the epidermis, several depth-dependent processes control the maintenance of the tight junction barrier during turnover, and induce the building, maintenance and degradation of the stratum corneum barrier. An understanding of these depth-dependent processes is required to study barrier homeostasis in physiological and pathological conditions. Adopting a modelling approach to integrate and compare available experimental data, a compartmental model of the stratum corneum is developed to characterise and visualise the resistance to water diffusion along its depth. The resulting resistance profiles, obtained from non-invasive confocal Raman spectroscopy and trans-epidermal water loss data, demonstrate a depth-dependent permeability barrier in the stratum corneum. Combined with models of barrier components and regulation of desquamation, the resistance profiles form a framework for studying stratum corneum barrier homeostasis. The selective permeability of the single-layered tight junction barrier is important in conserving specific environments on both sides of the barrier, which induce keratinocyte differentiation. In order to maintain its barrier function, the tight junctions have to be replaced continually while keratinocytes transition the barrier. Our 3D model of the stratum granulosum simulates the proposed mechanisms of barrier transition, and identifies how the temporal coordination of the transition ensures a constant barrier function. This thesis demonstrates how depth-dependent processes contribute to the regulation of both epidermal barriers in a continuously self-renewing tissue.
Supervisor: Tanaka, Reiko ; Parker, Kim Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral