A Model for Carrier-Mediated Biological Signal Transduction Based on Equilibrium Ligand Binding Theory
A Model for Carrier-Mediated Biological Signal Transduction Based on Equilibrium Ligand Binding Theory
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DOI：
10.1007/s11538-016-0173-1
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发表时间：
2016-05-01
影响因子：
3.5
通讯作者：
Schuetz, Stefan
中科院分区：
文献类型：
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作者：
Martini, Johannes W. R.;Schlather, Martin;Schuetz, Stefan
介绍了载体介导的信号转导数学模型的不同变体，重点介绍了昆虫嗅觉的气味剂量-电生理反应曲线。后者提供了一个独特的机会，可以通过实验观察载体分子组成的改变对信号分子依赖的响应曲线的影响。我们的工作强调了所涉及的载体分子的作用，这在过去的响应曲线数学模型中很大程度上被忽略了。由此产生的模型解释了在实验中观察到的信号分子运输中涉及多个载体分子如何导致剂量-反应曲线，而每个神经元不需要多个受体。特别地，该模型具有以下特点：(1)由一个受体和几个对信号分子具有不同亲和力的载体分子组成的系统实现了神经元反应的更大灵敏度范围。(2)考虑到不同载体分子的参与扩大了灵敏度范围，该模型表明，载体分子表达水平的强烈差异对于宽范围响应是绝对必要的。(3)不同载体分子之间的相互作用可以解释不同载体分子表达水平变化时剂量-响应曲线的复杂变化。我们在这里展示的电生理反应原理也可以应用于任何其他载体介导的生物信号转导过程。提出的概念为信号转导过程的建模和统计分析提供了一个框架，如果有足够的潜在生物学信息可用。
Different variants of a mathematical model for carrier-mediated signal transduction are introduced with focus on the odor dose-electrophysiological response curve of insect olfaction. The latter offers a unique opportunity to observe experimentally the effect of an alteration in the carrier molecule composition on the signal molecule-dependent response curve. Our work highlights the role of involved carrier molecules, which have largely been ignored in mathematical models for response curves in the past. The resulting model explains how the involvement of more than one carrier molecule in signal molecule transport can cause dose-response curves as observed in experiments, without the need of more than one receptor per neuron. In particular, the model has the following features: (1) An extended sensitivity range of neuronal response is implemented by a system consisting of only one receptor but several carrier molecules with different affinities for the signal molecule. (2) Given that the sensitivity range is extended by the involvement of different carrier molecules, the model implies that a strong difference in the expression levels of the carrier molecules is absolutely essential for wide range responses. (3) Complex changes in dose-response curves which can be observed when the expression levels of carrier molecules are altered experimentally can be explained by interactions between different carrier molecules. The principles we demonstrate here for electrophysiological responses can also be applied to any other carrier-mediated biological signal transduction process. The presented concept provides a framework for modeling and statistical analysis of signal transduction processes if sufficient information on the underlying biology is available.