Author/Editor		Gouveia, Marcos; Ikeshima-Kataoka, Hiroko; Zemljič Jokhadar, Špela; Vidak, Marko; Stojković, Biljana; Derganc, Jure; Travasso, Rui; Liović, Mirjana
Title		Keratin dynamics and spatial distribution in wild-type and K14 R125P mutant cells - a computational model
Type		članek
Vol. and No.		Letnik 21, št. 7
Publication year		2020
Volume		str. 1-13
ISSN		1422-0067 - International journal of molecular sciences
Language		eng
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.
Keywords		keratin epidermoliza bullosa simplex mutacija keratin epidermolysis bullosa simplex mutation