Keratin dynamics and spatial distribution in wild-type and K14 R125P mutant cells—a computational model

Gouveia, Marcos (author), Zemljič Jokhadar, Špela (author), Vidak, Marko (author), Stojković, Biljana (author), Derganc, Jure (author), Travasso, Rui (author), Liović, Mirjana (author)

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.

• Language: English
• Keywords: keratin, epidermolysis bullosa simplex, mutation, phase-field model, reaction-diffusion-advection equation
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: MF - Faculty of Medicine
• Publication status: Published
• Publication version: Version of Record
• Year: 2020
• Number of pages: 14 str.
• Numbering: Vol. 21, iss. 7, art. 2596
• PID: 20.500.12556/RUL-125685
• UDC: 61
• ISSN on article: 1422-0067
• DOI: 10.3390/ijms21072596
• COBISS.SI-ID: 34772697
• Publication date in RUL: 01.04.2021

Record is a part of a journal

• Title: International journal of molecular sciences
• Shortened title: Int. j. mol. sci.
• Publisher: MDPI
• ISSN: 1422-0067
• COBISS.SI-ID: 2779162

Licences

• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.
• Licensing start date: 09.04.2020

Secondary language

• Language: Slovenian
• Keywords: keratin, epidermoliza bullosa simplex, mutacija, model faznega polja, enačba reakcije-difuzije-advekcije