Visualization of signal transduction processes in the crowded environment of the cell

M. Falk, Michael Klann, M. Reuss, T. Ertl
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引用次数: 36

Abstract

In this paper, we propose a stochastic simulation to model and analyze cellular signal transduction. The high number of objects in a simulation requires advanced visualization techniques: first to handle the large data sets, second to support the human perception in the crowded environment, and third to provide an interactive exploration tool. To adjust the state of the cell to an external signal, a specific set of signaling molecules transports the information to the nucleus deep inside the cell. There, key molecules regulate gene expression. In contrast to continuous ODE models we model all signaling molecules individually in a more realistic crowded and disordered environment. Beyond spatiotemporal concentration profiles our data describes the process on a mesoscopic, molecular level, allowing a detailed view of intracellular events. In our proposed schematic visualization individual molecules, their tracks, or reactions can be selected and brought into focus to highlight the signal transduction pathway. Segmentation, depth cues and depth of field are applied to reduce the visual complexity. We also provide a virtual microscope to display images for comparison with wet lab experiments. The method is applied to distinguish different transport modes of MAPK (mitogen-activated protein kinase) signaling molecules in a cell. In addition, we simulate the diffusion of drug molecules through the extracellular space of a solid tumor and visualize the challenges in cancer related therapeutic drug delivery.
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细胞拥挤环境中信号转导过程的可视化
在本文中,我们提出了一个随机模拟来模拟和分析细胞信号转导。模拟中的大量对象需要先进的可视化技术:首先要处理大型数据集,其次要支持人类在拥挤环境中的感知,第三要提供交互式探索工具。为了调整细胞的状态以适应外部信号,一组特定的信号分子将信息传递到细胞深处的细胞核。在那里,关键分子调节基因表达。与连续ODE模型相比,我们在更现实的拥挤和无序环境中单独模拟所有信号分子。除了时空浓度曲线,我们的数据描述了中观、分子水平上的过程,允许对细胞内事件进行详细的观察。在我们提出的可视化示意图中,可以选择单个分子,它们的轨迹或反应,并将其纳入重点,以突出信号转导途径。分割,深度线索和景深的应用,以减少视觉复杂性。我们还提供了一个虚拟显微镜来显示图像,以与湿实验室实验进行比较。该方法用于区分细胞中MAPK(丝裂原活化蛋白激酶)信号分子的不同运输模式。此外,我们模拟了药物分子通过实体肿瘤细胞外空间的扩散,并可视化了癌症相关治疗药物递送的挑战。
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