Abstract
Keratins are one of the most abundant proteins in epithelial cells. They form a cytoskeletal filament network whose structural organization seriously conditions its function. Dynamic keratin particles and aggregates are often observed at the periphery of mutant keratinocytes related to the hereditary skin disorder epidermolysis bullosa simplex, which is due to mutations in keratins 5 and 14. To account for their emergence in mutant cells, we extended an existing mathematical model of keratin turnover in wild-type cells and developed a novel 2D phase-field model to predict the keratin distribution inside the cell. This model includes the turnover between soluble, particulate and filamentous keratin forms. We assumed that the mutation causes a slowdown in the assembly of an intermediate keratin phase into filaments, and demonstrated that this change is enough to account for the loss of keratin filaments in the cell’s interior and the emergence of keratin particles at its periphery. The developed mathematical model is also particularly tailored to model the spatial distribution of keratins as the cell changes its shape.
Highlights
The epidermis is the multilayered outer layer of skin, which functions as a protective barrier to all internal tissues and organs
With the aim of providing some visual background information that has led to the development of our improved keratin dynamics mathematical model, we performed a few in vitro experiments, which portray some of the main findings already published on keratin filament dynamics
In this paper we have implemented a mathematical model of the keratin turnover in mutant cells that accounts for the appearance of keratin particles at the cell’s periphery
Summary
The epidermis is the multilayered outer layer of skin, which functions as a protective barrier to all internal tissues and organs. It consists of very tightly packed epithelial cells called keratinocytes. The cytoskeleton of keratinocytes includes keratin intermediate filament (IF) proteins. These are essential to cells since they provide mechanical resilience [1,2,3,4], but are involved in many cell and tissue functions such as cell growth, proliferation, wound healing, migration, etc. Epidermal keratins are divided into type I and type II proteins. ULFs associate longitudinally (end-to-end) to form shorter filaments, which can subsequently anneal longitudinally to build longer filaments [22]
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