Frontiers in epidermal barrier homeostasis – an approach to mathematical modelling of epidermal calcium dynamics

Abstract

Intact epidermal barrier function is crucial for survival and is associated with the presence of gradients of both calcium ion concentration and electric potential. Although many molecules, including ion channels and pumps, are known to contribute to maintenance of these gradients, the mechanisms involved in epidermal calcium ion dynamics have not been clarified. We have established that a variety of neurotransmitters and their receptors, originally found in the brain, are expressed in keratinocytes and are also associated with barrier homeostasis. Moreover, keratinocytes and neurons show some similarities of electrochemical behaviour. As mathematical modelling and computer simulation have been employed to understand electrochemical phenomena in brain science, we considered that a similar approach might be applicable to describe the dynamics of epidermal electrochemical phenomena associated with barrier homeostasis. Such methodology would also be potentially useful to address a number of difficult problems in clinical dermatology, such as ageing and itching. Although this work is at a very early stage, in this essay, we discuss the background to our approach and we present some preliminary results of simulation of barrier recovery.

Endoplasmic Reticulum Calcium Regulates Epidermal Barrier Response and Desmosomal Structure

“…Several experimental (Celli et al, 2010; Jungman et al, 2012; Mauro et al, 1998; Menon et al, 1992; Tsutsumi et al, 2009) and computational approaches (Adams et al, 2012, 2015; Cornelissen et al, 2007; Denda et al, 2014) have been used to model or measure Ca 2+ fluxes in epidermis. While initial studies using fixed and sectioned tissue (Mauro et al, 1998; Menon et al, 1992) showed that after acute barrier perturbation, Ca 2+ drops in the viable layers and then recovers as the barrier recovers, a more recent study (Behne et al, 2011) reported a moderate increase in intracellular and extracellular calcium concentration as soon as 30 minutes after barrier perturbation by acetone lipid extraction in hairless mice.…”

Role of STIM1–Orai1 system in intra‐cellular calcium elevation induced by ATP in cultured human keratinocytes

“…We recently presented a mathematical model of the epidermal barrier homoeostasis (5). ATP plays a crucial role in cell-cell communication in this model, based on our previous findings that ATP was released after disruption of the epidermal permeability barrier of intact skin or on exposure of cultured keratinocytes to air, and also that application of suramin, a blocker of purinergic receptors, accelerated barrier recovery of the skin and blocked [Ca 2+ ] i elevation (1,2).…”

Interplay between epidermal stem cell dynamics and dermal deformation

“…Skin is an important organ that provides us with barriers such as protecting from damages and preventing dehydration [20,21], and its internal structure affects barrier functions: for example, diseases such as psoriasis are accompanied by altered structure of the epidermaldermal interface, where the germinative cell population increases and their activity is enhanced [22,23]. Al- though mathematical models have been proposed to understand skin barrier functions [24][25][26][27][28][29][30][31][32], the morphology of the epidermal-dermal interface and its relationship to stem cell patterning has been largely ignored, except for a speculation on the interplay between stem cell activities and the dermal structure [33].…”