Corneocytes as potential biomarkers of skin integrity

Marques Mendes Evora, Ana Sofia ORCID: 0000-0003-1562-6105 (2023). Corneocytes as potential biomarkers of skin integrity. University of Birmingham. Ph.D.

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Abstract

A healthy skin barrier is crucial for protecting against environmental threats and maintaining skin health. Pressure ulcers (PUs) remain a prevalent issue in European hospitals (around 11% incidence). This thesis investigates the role of the stratum corneum (SC) and corneocytes in early skin damage and PU development.

To accurately measure corneocyte mechanical properties, a meticulous protocol using Atomic Force Microscopy nanoindentation was developed. Corneocytes exhibited Young's moduli (~0.4–1.5 GPa) similar to glassy organic polymers and, at stresses greater than the yield value, they displayed viscoplastic behaviour describable by the Herschel-Bulkley model. Immersed in water, corneocytes swelled, becoming more compliant (~2 MPa), less rigid, and more strain-tolerant. In-depth analysis of corneocytes from different anatomical sites revealed variations in topography, cornified envelope (CE) maturity, and corneodesmosome distribution, indirectly assessed through desmoglein-1 staining (Dsg1). Corneocytes from the volar forearm, neck, and sacrum had similar topographies, CE maturity (17–20%), and Dsg1 expression (18–24%). Cheek cells presented circular nano-objects and increased Dsg1 levels (46%). Medial heel cells displayed villi-like structures, along with high levels of immature CEs (48%) and Dsg1 (68%). The cell stiffness showed significant inter-subject variability, correlating with the level of immature CEs at the cheek, neck, and sacrum.

Two cohort studies investigated corneocyte properties in the context of skin integrity: in respirator usage among healthcare professionals during the COVID-19 pandemic and in category I PUs. The first study linked elevated levels of immature CEs to self-reported adverse reactions. The second study observed differences in cell topography, immature CEs, and corneodesmosome distribution in category I PUs, indicating the presence of immature SC markers even in early skin damage. Although no significant variations in Young’s modulus were found, corneocytes from elderly patients tended to be more compliant than those from young individuals (patient cells: ~0.05–0.60 GPa).

Together, these findings contribute to our understanding of the properties of corneocyte and skin mechanical and barrier functions and are the first step in investigating the potential of using superficial skin cells as prediction and/or diagnostic markers for early skin damage.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):