Keratin Dynamics and Spatial Distribution in Wild-Type and K14 R125P Mutant Cells—A Computational Model
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 hereditar...
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MDPI AG
2020-04-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/7/2596 |
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| author | Marcos Gouveia Špela Zemljič-Jokhadar Marko Vidak Biljana Stojkovič Jure Derganc Rui Travasso Mirjana Liovic |
| author_facet | Marcos Gouveia Špela Zemljič-Jokhadar Marko Vidak Biljana Stojkovič Jure Derganc Rui Travasso Mirjana Liovic |
| author_sort | Marcos Gouveia |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T20:35:57Z |
| format | Article |
| id | doaj.art-8c5d94e0d94c43cd8fe59e1d760b6eb3 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T20:35:57Z |
| publishDate | 2020-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-8c5d94e0d94c43cd8fe59e1d760b6eb32023-11-19T21:04:16ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-04-01217259610.3390/ijms21072596Keratin Dynamics and Spatial Distribution in Wild-Type and K14 R125P Mutant Cells—A Computational ModelMarcos Gouveia0Špela Zemljič-Jokhadar1Marko Vidak2Biljana Stojkovič3Jure Derganc4Rui Travasso5Mirjana Liovic6CFisUC, Center for Physics of the University of Coimbra, Department of Physics, University of Coimbra, R Larga, 3004-516 Coimbra, PortugalInstitute for Biophysics, Faculty of Medicine, University of Ljubljana, Vrazov trg 2, 1000 Ljubljana, SloveniaMedical Center for Molecular Biology, Institute for Biochemistry, Faculty of Medicine, University of Ljubljana, Vrazov trg 2, 1000 Ljubljana, SloveniaInstitute for Biophysics, Faculty of Medicine, University of Ljubljana, Vrazov trg 2, 1000 Ljubljana, SloveniaInstitute for Biophysics, Faculty of Medicine, University of Ljubljana, Vrazov trg 2, 1000 Ljubljana, SloveniaCFisUC, Center for Physics of the University of Coimbra, Department of Physics, University of Coimbra, R Larga, 3004-516 Coimbra, PortugalMedical Center for Molecular Biology, Institute for Biochemistry, Faculty of Medicine, University of Ljubljana, Vrazov trg 2, 1000 Ljubljana, SloveniaKeratins 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.https://www.mdpi.com/1422-0067/21/7/2596keratinepidermolysis bullosa simplexmutationphase-field modelreaction-diffusion-advection equation |
| spellingShingle | Marcos Gouveia Špela Zemljič-Jokhadar Marko Vidak Biljana Stojkovič Jure Derganc Rui Travasso Mirjana Liovic Keratin Dynamics and Spatial Distribution in Wild-Type and K14 R125P Mutant Cells—A Computational Model International Journal of Molecular Sciences keratin epidermolysis bullosa simplex mutation phase-field model reaction-diffusion-advection equation |
| title | Keratin Dynamics and Spatial Distribution in Wild-Type and K14 R125P Mutant Cells—A Computational Model |
| title_full | Keratin Dynamics and Spatial Distribution in Wild-Type and K14 R125P Mutant Cells—A Computational Model |
| title_fullStr | Keratin Dynamics and Spatial Distribution in Wild-Type and K14 R125P Mutant Cells—A Computational Model |
| title_full_unstemmed | Keratin Dynamics and Spatial Distribution in Wild-Type and K14 R125P Mutant Cells—A Computational Model |
| title_short | Keratin Dynamics and Spatial Distribution in Wild-Type and K14 R125P Mutant Cells—A Computational Model |
| title_sort | keratin dynamics and spatial distribution in wild type and k14 r125p mutant cells a computational model |
| topic | keratin epidermolysis bullosa simplex mutation phase-field model reaction-diffusion-advection equation |
| url | https://www.mdpi.com/1422-0067/21/7/2596 |
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