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Numerical analysis of mesenchymal stem cell mechanotransduction dynamics reveals homoclinic bifurcations

机译:间充质干细胞机械调节动力学的数值分析揭示了同型分岔

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We perform one and two-parameter numerical bifurcation analysis of a mechanotransduction model approximating the dynamics of mesenchymal stem cell differentiation into neurons, adipocytes, myocytes and osteoblasts. For our analysis, we use as bifurcation parameters the stiffness of the extracellular matrix and parameters linked with the positive feedback mechanisms that up-regulate the production of the YAP/TAZ transcriptional regulators (TRs) and the cell-substrate adhesion area. Our analysis reveals regimes of hysteresis and multistability, stable oscillations of the effective adhesion area, the YAP/TAZ TRs and the PPAR gamma receptors associated with the adipogenic fate, as well as homoclinic bifurcations that interrupt high-amplitude oscillations abruptly. The two-parameter bifurcation analysis of the Andronov-Hopf points that give birth to the oscillating patterns predicts their existence for soft extracellular substrates ( 1kPa), a regime that favours the neurogenic and the adipogenic cell fate. Furthermore, in these regimes, the analysis reveals the presence of homoclinic bifurcations that result in the sudden loss of stable oscillations of the cell-substrate adhesion towards weaker adhesions and high expression levels of the gene encoding Tubulin beta-3 chain, thus favouring the phase transition from the adipogenic to the neurogenic fate.
机译:我们执行近似间充质干细胞分化为神经元,脂肪细胞,肌细胞和成骨细胞动态的机制模型的一个和两个参数数值分析。为了我们的分析,我们使用的是分叉参数的细胞外基质的刚度和与阳性反馈机制相关的参数,以上调节YAP / TAZ转录调节剂(TRS)和细胞基板粘附区域的产生。我们的分析揭示了滞后和多个能力的制度,有效粘附区域的稳定振荡,YAP / TAZ TRS和与脂肪生物命运相关的PPARγ受体,以及突然中断高幅度振荡的同型分叉。生育振荡模式的Andronov-Hopf点的双参数分岔分析预测它们对软细胞外衬底(<1kPa)的存在,这是一种促进神经源性和脂肪组细胞命运的制度。此外,在这些制度中,分析揭示了同型分叉的存在,导致细胞基板粘附稳定振荡的突然损失,朝向编码小管蛋白β-3链的基因的较弱和高表达水平,因此有利于相位从脂肪生成到神经源性命运的转变。

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