Application of circuit simulation method for differential modeling of TIM-2 iron uptake and metabolism in mouse kidney cells.
Application of circuit simulation method for differential modeling of TIM-2 iron uptake and metabolism in mouse kidney cells.
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DOI：
10.3389/fphys.2013.00136
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发表时间：
2013
影响因子：
4
通讯作者：
Han J
中科院分区：
文献类型：
--
作者：
Xie Z;Harrison SH;Torti SV;Torti FM;Han J
电路仿真是一种生成微分数学模型的强大方法。由于其高精度的建模能力，电路仿真可以用来研究蜂窝系统的部件和过程之间的相互作用。电路仿真已成为电气工程领域的一项核心技术，但其在生物学中的应用尚未完全实现。作为评估高级设计系统(ADS)电路仿真工具更高级功能的案例研究，我们收集并模拟了小鼠肾脏细胞中铁代谢的H铁蛋白(HFT)受体、T细胞免疫球蛋白和粘蛋白结构域-2(TIM-2)的实验室数据。提取TIM-2相关铁代谢的内控参数，并用ADS定量计算细胞间的铁移动率。通过电路模拟处理的差异模型显示了识别变量和预测结果的能力，这些变量和结果无法通过体外实验轻松测量。例如，载铁高铁FT的初始摄取率(Fe-HFT)为每百万个细胞2.17pmoL。TIM-2与Fe-HFT结合的几率为16.6%。TIM-2与Fe-HFT形成复合体平均需要8.5min。内吞作用结束时，约有28%的HFT保持完好，其余的降解。降解的HFT释放出的铁进入不稳定的铁库(LIP)，并刺激内源HFT的产生以供新的储存。实验数据和模型均表明TIM-2不参与铁的输出过程。提取的内部控制参数成功地捕捉到了TIM-2通路的复杂性，下一步是使用基于电路仿真的更广泛的蜂窝系统建模来验证该方法的意义和实用性。
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.
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影响因子：
6.5
作者：
KONIJN, AM;CARMEL, N;HERSHKO, C
通讯作者：
HERSHKO, C
影响因子：
56.9
作者：
MCADAMS, HH;SHAPIRO, L
通讯作者：
SHAPIRO, L
DOI：
10.1093/imammb/dqq021
发表时间：
2012-03-01
影响因子：
1.1
作者：
Rejniak, Katarzyna A.;Quaranta, Vito;Anderson, Alexander R. A.
通讯作者：
Anderson, Alexander R. A.
影响因子：
--
作者：
Salgado JC;Olivera-Nappa A;Gerdtzen ZP;Tapia V;Theil EC;Conca C;Nuñez MT
通讯作者：
Nuñez MT
影响因子：
7.7
作者：
Meier, J;Wölkhammer, S;Habler, O
通讯作者：
Habler, O