成骨细胞力学信号转导通路的ABM：关键事件的时间模式
ABM of osteoblast's mechanotransduction pathway: time patterns of critical events
摘要：
背景：骨细胞的力学信号转导在成骨细胞分化和骨重建中起关键作用。机械转导提供了细胞外基质的调节和细胞内作用之间的联系。通过控制细胞内和细胞外结构域之间的平衡，机械力转导过程决定了骨骼动力学的最佳功能，并且它是骨病的可能原因之一。结果如下：在一个单一的成骨细胞在外部机械扰动下的机械转导已建模的代理为基础的框架，以再现在细胞质，核和细胞外结构域的分子之间的随机反应扩散过程的动力学。分子量和波动的每个分子类已被分析的关键事件的复发方面。一个数值方法已被开发来反转从属过程，并提取的分子信号，以获得事件的复发分布的指导过程。结论：我们观察到大的波动包含隐藏在噪声中的信息，这些信息超出了分子基线的动态变化。在不同的参数条件和刺激下研究系统，结果表明，每个分子的等待时间分布是系统动力学的签名。分子等待时间的行为随着参数的变化而变化，对于相似的相互作用分子呈现相同的模式变化，并且识别机械转导途径中的关键分子的特定改变。
英文摘要：
Background: Mechanotransduction in bone cells plays a pivotal role in osteoblast differentiation and bone remodelling. Mechanotransduction provides the link between modulation of the extracellular matrix and intracellular actions. By controlling the balance between the intracellular and extracellular domains, the mechanotransduction process determines optimal functionality of the skeletal dynamics, and it is one of the possible causes of osteophatological diseases. Results: Mechanotransduction in a single osteoblast under external mechanical perturbations has been modelled in the agent based framework to reproduce the dynamics of the stochastic reaction diffusion process among molecules in the cytoplasm, nuclear and extracellular domains. The amount of molecules and fluctuations of each molecular class has been analysed in terms of recurrences of critical events. A numerical approach has been developed to invert subordination processes and to extract the directing processes from the molecular signals in order to derive the distribution of recurrence of events. Conclusions: We observed large fluctuations enclose information hidden in the noise which is beyond the dynamic variations of molecular baselines. Studying the system under different parametric conditions and stimuli, the results have shown that the waiting time distributions of each molecule are a signature of the system's dynamics. The behaviours of the molecular waiting times change with the changing of parameters presenting the same variation of patterns for similar interacting molecules and identifying specific alterations for key molecules in the mechanotransduction pathway.
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