CFisUC, Center for Physics of the University of Coimbra, Department of Physics, University of Coimbra, R Larga, 3004-516 Coimbra, Portugal.
Institute for Biophysics, Faculty of Medicine, University of Ljubljana, Vrazov trg 2, 1000 Ljubljana, Slovenia.
Int J Mol Sci. 2020 Apr 9;21(7):2596. doi: 10.3390/ijms21072596.
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.
角蛋白是上皮细胞中含量最丰富的蛋白质之一。它们形成细胞骨架丝状网络，其结构组织严重影响其功能。在与遗传性皮肤疾病单纯性大疱性表皮松解症相关的突变角朊细胞的外周，经常观察到动态角蛋白颗粒和聚集体，这是由于角蛋白 5 和 14 的突变所致。为了解释它们在突变细胞中的出现，我们扩展了野生型细胞中角蛋白周转的现有数学模型，并开发了一种新的 2D 相场模型来预测细胞内角蛋白的分布。该模型包括可溶性、颗粒状和丝状角蛋白形式之间的转化。我们假设突变导致中间角蛋白相组装成丝状的速度减慢，并证明这种变化足以解释细胞内部角蛋白丝的丢失和细胞外周角蛋白颗粒的出现。所开发的数学模型还特别适合于模拟细胞形状变化时角蛋白的空间分布。
