Computational model provides insight into the distinct responses of neurons to chemical and topographical cues.
Computational model provides insight into the distinct responses of neurons to chemical and topographical cues.
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DOI：
10.1007/s10439-008-9613-x
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发表时间：
2009-02
影响因子：
3.8
通讯作者：
Zaman, Muhammad H.
中科院分区：
文献类型：
--
作者：
Forciniti, Leandro;Schmidt, Christine E.;Zaman, Muhammad H.
神经元细胞极化（即，轴突的建立）和轴突引导由来自环境的机械和化学信号介导和控制。不幸的是，一个综合的方法来研究细胞基质相互作用在一个统一的框架，结合结构和化学效应的基板一直缺乏。在本文中，我们提出了一个新的模型相结合的实验和计算方法，以更好地了解不同的行为E18海马神经元的地形与固定化学线索。我们提出的结果，从我们的粗粒度生理计算模型，正确地描述了以前观察到的现象和预测的行为，随后通过新的实验进行了测试。该模型区分地形化学线索通过线索间距在这两个基板的差异。使用地形线索的特征尺寸间距和最小步长，由物理学的丝状伪足突起，化学线索，该模型成功地模拟了实验极化概率为四个不同的地形特征尺寸和恒定的化学线索间距观察到的趋势。我们的研究结果不仅显示出良好的协议与实验，但也提供了新的建议，开发基板更精细的控制神经细胞的极化。
Neuronal cell polarization (i.e., establishment of an axon) and axon guidance are mediated and controlled by mechanical and chemical signals from the environment. Unfortunately, an integrated approach to study cell–substrate interactions in a unified framework incorporating structural and chemical effects of the substrate has been lacking. In this paper, we present a new model combining experimental and computational methods to better understand the distinct behavior of E18 hippocampal neurons in response to topographical vs. immobilized chemical cues. We present results from our coarse-grain physiological computational model that correctly describes previously observed phenomena and predicts behavior that was subsequently tested through new experiments. The model differentiates topographical from chemical cues via a difference in cue spacing in these two substrates. Using the feature size spacing for topographical cues and a minimum step size, governed by the physics of filopodia protrusion, for chemical cues, the model successfully mimics the trend observed in experimental polarization probability for four different topographical feature sizes and constant chemical cue spacing. Our results not only show good agreement with experiments, but also provide novel suggestions for development of substrates for finer control of neuronal cell polarization.
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