Keratin dynamics: modeling the interplay between turnover and transport

Portet S, Madzvamuse A, Chung A, Leube RE, Windoffer R

Keratin are among the most abundant proteins in epithelial cells. Functions of the keratin network in cells are shaped by their dynamical organization. Using a collection of experimentally-driven mathematical models, different hypotheses for the turnover and transport of the keratin material in epithelial cells are tested. The interplay between turnover and transport and their effects on the keratin organization in cells are hence investigated by combining mathematical modeling and experimental data.

Amongst the collection of mathematical models considered, a best model strongly supported by experimental data is identified. Fundamental to this approach is the fact that optimal parameter values associated with the best fit for each model are established. The best candidate among the best fits is characterized by the disassembly of the assembled keratin material in the perinuclear region and an active transport of the assembled keratin. Our study shows that an active transport of the assembled keratin is required to explain the experimentally observed keratin organization.

Time-lapse fluorescence microscopy of hepatocellular carcinoma-derived PLC clone PK18-5 stably expressing fluorescent fusion protein HK18-YFP [8] depicting the dynamic properties of the keratin filaments over a time period of 15 hours. Bar 10 μm.

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