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Title: A mathematical model for the dependence of keratin aggregate formation on the quantity of mutant keratin expressed in EGFP-K14 R125P keratinocytes
Authors: Gouveia, Marcos 
Sorčan, Tjaša
Zemljič-Jokhadar, Špela
Travasso, Rui D.M. 
Liović, Mirjana
Issue Date: 2021
Publisher: Public Library of Science
Project: SFRH/BD/136046/ 2018 
UIDB/04564/ 2020 
CELSA Alliance and ARRS J3-3078 grants to M.L., the Slovenian Research Agency Program Grant P1- 0390, and the Republic of Slovenia Ministry of Education, Science and Sport and the EraCoSysMed (JTC-2 2017) “4D-HEALING” grant” 
Serial title, monograph or event: PLoS ONE
Volume: 16
Issue: 12
Abstract: We examined keratin aggregate formation and the possible mechanisms involved. With this aim, we observed the effect that different ratios between mutant and wild-type keratins expressed in cultured keratinocytes may have on aggregate formation in vitro, as well as how keratin aggregate formation affects the mechanical properties of cells at the cell cortex. To this end we prepared clones with expression rates as close as possible to 25%, 50% and 100% of the EGFP-K14 proteins (either WT or R125P and V270M mutants). Our results showed that only in the case of the 25% EGFP-K14 R125P mutant significant differences could be seen. Namely, we observed in this case the largest accumulation of keratin aggregates and a significant reduction in cell stiffness. To gain insight into the possible mechanisms behind this observation, we extended our previous mathematical model of keratin dynamics by implementing a more complex reaction network that considers the coexistence of wild-type and mutant keratins in the cell. The new model, consisting of a set of coupled, non-linear, ordinary differential equations, allowed us to draw conclusions regarding the relative amounts of intermediate filaments and aggregates in cells, and suggested that aggregate formation by asymmetric binding between wild-type and mutant keratins could explain the data obtained on cells grown in culture.
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0261227
Rights: openAccess
Appears in Collections:I&D CFis - Artigos em Revistas Internacionais

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