Stochastic models of receptor oligomerization by bivalent ligand
Stochastic models of receptor oligomerization by bivalent ligand
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DOI：
10.1098/rsif.2006.0116
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发表时间：
2006-08-22
影响因子：
3.9
通讯作者：
Page, Karen M.
中科院分区：
文献类型：
--
作者：
Alarcon, Tomas;Page, Karen M.
在本文中，我们开发的受体结合的二价配体的随机模型。一个详细的动力学研究使我们能够分析的作用，通过受体寡聚化的细胞活化的交联。我们展示了寡聚体的形成如何缓冲细胞内信号的随机波动。此外，我们提出的假设，即形成长的线性低聚物增加了细胞响应的配体浓度的范围，而形成封闭的低聚物增加了配体浓度的特异性。因此，需要对配体浓度具有不同程度特异性的不同生理功能将有利于形成具有不同长度和几何形状的寡聚体。此外，只要配体浓度特异性作为设计原则，我们的模型使我们能够估计参数，如受体的最小比例，必须从事寡聚体形成，以触发细胞反应。
In this paper, we develop stochastic models of receptor binding by a bivalent ligand. A detailed kinetic study allows us to analyse the role of cross-linking in cell activation by receptor oligomerization. We show how oligomer formation could act to buffer intracellular signalling against stochastic fluctuations. In addition, we put forward the hypothesis that formation of long linear oligomers increases the range of ligand concentration to which the cell is responsive, whereas formation of closed oligomers increases ligand concentration specificity. Thus, different physiological functions requiring different degrees of specificity to ligand concentration would favour formation of oligomers with different lengths and geometries. Furthermore, provided that ligand concentration specificity is taken as a design principle, our model enables us to estimate parameters, such as the minimum proportion of receptors, that must engage in oligomer formation in order to trigger a cellular response.