Quantitative single-molecule localization microscopy combined with rule-based modeling reveals ligand-induced TNF-R1 reorganization toward higher-order oligomers
Quantitative single-molecule localization microscopy combined with rule-based modeling reveals ligand-induced TNF-R1 reorganization toward higher-order oligomers
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DOI：
10.1007/s00418-014-1195-0
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发表时间：
2014-07-01
影响因子：
2.3
通讯作者：
Heilemann, Mike
中科院分区：
文献类型：
--
作者：
Fricke, Franziska;Malkusch, Sebastian;Heilemann, Mike
我们报告的装配肿瘤坏死因子受体1（TNF-R1）配体激活和其配体诱导的重组细胞膜之前。我们应用单分子定位显微镜获得受体簇大小和拷贝数的定量信息。我们的数据表明，TNF-R1的二聚体预组装，以及受体重组向更高的寡聚状态与稳定的人口包括三至六个TNF-R1。我们的实验结果直接作为输入参数的配体-受体相互作用的计算建模。模拟证实了高阶低聚态的实验结果。这项工作首次展示了定量，超分辨率和先进的显微镜如何用于单分子和单细胞水平的系统生物学方法。
We report on the assembly of tumor necrosis factor receptor 1 (TNF-R1) prior to ligand activation and its ligand-induced reorganization at the cell membrane. We apply single-molecule localization microscopy to obtain quantitative information on receptor cluster sizes and copy numbers. Our data suggest a dimeric pre-assembly of TNF-R1, as well as receptor reorganization toward higher oligomeric states with stable populations comprising three to six TNF-R1. Our experimental results directly serve as input parameters for computational modeling of the ligand-receptor interaction. Simulations corroborate the experimental finding of higher-order oligomeric states. This work is a first demonstration how quantitative, super-resolution and advanced microscopy can be used for systems biology approaches at the single-molecule and single-cell level.