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首页> 美国卫生研究院文献>Frontiers in Physiology >Application of circuit simulation method for differential modeling of TIM-2 iron uptake and metabolism in mouse kidney cells
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Application of circuit simulation method for differential modeling of TIM-2 iron uptake and metabolism in mouse kidney cells

机译：电路仿真方法在小鼠肾细胞中TIM-2铁吸收和代谢差异建模的应用

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Circuit simulation is a powerful methodology to generate differential mathematical models. Due to its highly accurate modeling capability, circuit simulation can be used to investigate interactions between the parts and processes of a cellular system. Circuit simulation has become a core technology for the field of electrical engineering, but its application in biology has not yet been fully realized. As a case study for evaluating the more advanced features of a circuit simulation tool called Advanced Design System (ADS), we collected and modeled laboratory data for iron metabolism in mouse kidney cells for a H ferritin (HFt) receptor, T cell immunoglobulin and mucin domain-2 (TIM-2). The internal controlling parameters of TIM-2 associated iron metabolism were extracted and the ratios of iron movement among cellular compartments were quantified by ADS. The differential model processed by circuit simulation demonstrated a capability to identify variables and predict outcomes that could not be readily measured by in vitro experiments. For example, an initial rate of uptake of iron-loaded HFt (Fe-HFt) was 2.17 pmol per million cells. TIM-2 binding probability with Fe-HFt was 16.6%. An average of 8.5 min was required for the complex of TIM-2 and Fe-HFt to form an endosome. The endosome containing HFt lasted roughly 2 h. At the end of endocytosis, about 28% HFt remained intact and the rest was degraded. Iron released from degraded HFt was in the labile iron pool (LIP) and stimulated the generation of endogenous HFt for new storage. Both experimental data and the model showed that TIM-2 was not involved in the process of iron export. The extracted internal controlling parameters successfully captured the complexity of TIM-2 pathway and the use of circuit simulation-based modeling across a wider range of cellular systems is the next step for validating the significance and utility of this method.
机译：电路仿真是生成微分数学模型的强大方法。由于其高度精确的建模能力，电路仿真可用于研究蜂窝系统各部分和过程之间的相互作用。电路仿真已经成为电气工程领域的一项核心技术，但尚未完全实现其在生物学中的应用。作为评估称为高级设计系统（ADS）的电路仿真工具的更高级功能的案例研究，我们收集并建模了小鼠肾脏细胞中铁蛋白H（HFt）受体，T细胞免疫球蛋白和粘蛋白的铁代谢的实验室数据。域2（TIM-2）。提取了TIM-2相关铁代谢的内部控制参数，并通过ADS定量测定了铁在各细胞间的移动比例。通过电路仿真处理的差分模型证明了具有识别变量和预测结果的能力，而这些变量是体外实验无法轻易测量的。例如，铁吸收的HFt（Fe-HFt）的初始摄取率为每百万细胞2.17 pmol。 TIM-2与Fe-HFt的结合概率为16.6％。 TIM-2和Fe-HFt的复合物形成内体平均需要8.5分钟。含HFt的内体持续约2小时。在内吞作用结束时，约28％的HFt保持完整，其余的则降解。降解的HFt释放出的铁在不稳定的铁池（LIP）中，并刺激了内源性HFt的生成，可用于新的存储。实验数据和模型均表明TIM-2不参与铁的出口过程。提取的内部控制参数成功地捕获了TIM-2通路的复杂性，并且在更广泛的蜂窝系统中使用基于电路仿真的建模是验证该方法的重要性和实用性的下一步。

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