A Computational Model of the Epidermis With the Deformable Dermis and Its Application to Skin Diseases

Abstract

The skin barrier is provided by the organized multi-layer structure of epidermal cells, which is dynamically maintained by a continuous supply of cells from the basal layer. The epidermal homeostasis can be disrupted by various skin diseases, which often cause morphological changes not only in the epidermis but in the dermis. We present a three-dimensional agent-based computational model of the epidermis that takes into account the deformability of the dermis. Our model can produce a stable epidermal structure with well-organized layers. We show that its stability depends on the cell supply rate from the basal layer. Modeling the morphological change of the dermis also enables us to investigate how the stiffness of the dermis affects the structure and barrier functions of the epidermis. Besides, we show that our model can simulate the formation of a corn (clavus) by assuming hyperproliferation and rapid differentiation. We also provide experimental data for human corn, which supports the model assumptions and the simulation result.

AQP5 pathogenic variants induce palmoplantar keratoderma Bothnia type in two Chinese families

“…This abnormal expression pattern of Ki67, K14, and K10 indicated that excessive keratinocyte proliferation likely resulted in fast differentiation and immature differentiation. 8 TRPV4 can physically interact with AQP5 to form a functional complex controlling osmotic stress. 9 Cao et al 5 studied the AQP5Asn123Tyr variant and found that the AQP5Asn123Tyr/TRPV4 complex in keratinocytes had a stronger function than control.…”

“…Keratin K14, K10, and loricrin are the main structural protein products of basal, spinous, and granular layers, respectively. This abnormal expression pattern of Ki67, K14, and K10 indicated that excessive keratinocyte proliferation likely resulted in fast differentiation and immature differentiation 8 …”

Individualised computational modelling of immune mediated disease onset, flare and clearance in psoriasis

“…Over the past twenty years several papers have reported agent-based models of human epidermis formation and homeostasis [52, 25, 2, 53, 41]. However, due in part to the disease complexity and to the difficulty of obtaining clinical data, there are few publications addressing the computational modelling of psoriasis and its treatment.…”

Modeling the extracellular matrix in cell migration and morphogenesis: a guide for the curious biologist

“…During development, the mammalian skin BM changes from an initially flat surface to an undulated one (Shen et al, 2023). In this context, the interaction between cell proliferation and the ECM is also the focus of several models where the BM is represented as a collection of small spheres (Kobayashi et al, 2018;Ohno et al, 2021). The authors argue that mechanical buckling alone cannot explain undulation, as buckling neither gives a direction of undulation nor does it lead to irregular undulations, as observed in the skin.…”

“…In addition, the positioning of stem cells along the 2017), cell growth can compress strands of initially loose ECM to form thick septa. In the skin, cell proliferation may underlie the formation of undulations in the BM (Kobayashi et al, 2018;Ohno et al, 2021).…”