Image-based modelling of cell reorientation
Image-based modelling of cell reorientation
复制标题
基于图像的细胞重定向建模
DOI：
--
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
R. Lockley
中科院分区：
文献类型：
--
作者：
R. Lockley
定向细胞运动在生物学的许多领域中起着关键作用，细胞能够对细胞外刺激的变化做出快速的重新定位。一个复杂的信令网络引导着这种反应，这促使使用概念性数学模型来复制这种行为的各个方面，并且可以更容易地进行分析。这些模型之间的比较更多地集中在它们之间的质量差异上。我们希望构建一个框架，用于模型之间的严格比较，使用细胞重新极化来响应剪切率变化。
我们将三种细胞极性的反应-扩散模型与实验数据进行了拟合，该实验数据反映了机械剪切流引起的变形网柄线虫的复极。在不同条件下进行的实验被同时拟合，以提供具有一系列细胞动力学的模型，这些模型适合F-肌动蛋白报告器的皮层荧光的时空数据。所有模型都能给出令人满意的t检验，参数可辨识性用概率似然法确定。Meinhardt和Levchenko模型能够获得比Otsuji模型更好的拟合。对模型行为和参数可辨识性的分析促使模型发生改变，这导致了一个完全可辨认的双变量Meinhardt模型。
迈因哈特和列夫琴科模型的模拟被用来测试它们在模型拟合后的时间范围内的行为。这促使模型参数发生变化，以获得所需的长期行为。运行进一步的模拟以引起模型对除了在拟合中看到的变化的外部信号的响应，模型能够适应移动信号，并对多个同时信号做出响应。
使用单细胞数据对Meinhardt和Levchenko模型进行了进一步的拟合。这些模型能够很好地测试来自复极化和未刺激细胞的数据，表明这些模型能够复制平均和单细胞时空成像数据。
Directed cell motility plays a key role in many areas of biology, with cells able to reorient quickly in response to changes of an extracellular stimuli. A complex signalling network directs this response, which motivates the use of conceptual mathematical models that replicate aspects of this behaviour and can be more readily analysed. Comparisons between such models have more focused on the qualitative differences between them. We wished to construct a framework for the rigorous comparison between models, using cell repolarisation in response to shear ow change.
We fitted three reaction-diffusion models of cell polarity to experimental data of dictyostelium amoeba repolarising in response to mechanical shear flow. Experiments performed under different conditions were fitted simultaneously, to provide models with a range of cellular dynamics, with the models being fit to spatio-temporal data of cortex fluorescence of an F-actin reporter. All models were able to give a satisfactory t, with parameter identifiability determined using the pro le likelihood. The Meinhardt and Levchenko models were able to obtain better fits than the Otsuji model. Analysis of the model behaviour and parameter identifiability prompted alterations of the models, which resulted in a fully identi able two-variable Meinhardt model.
Simulations of the Meinhardt and Levchenko models were used to test their behaviour over time frames past which the models had been tfitted. This motivated changes to the model parameters to obtain the desired long-term behaviour. Further simulations were run to elicit the model response to a changing external signal beyond that seen in the fitting, with the models being able to adapt to a moving signal, and respond to multiple simultaneous signals.
Further fitting of the Meinhardt and Levchenko models was conducted using single cell data. The models were able to t well to data taken from both repolarising and unstimulated cells, showing that these models are able to replicate both mean and single cell spatio-temporal imaging data.
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影响因子：
3.3
作者：
Lee, S;Comer, FI;Firtel, RA
通讯作者：
Firtel, RA
人中性粒细胞上甲酰基肽受体成分的分离和部分表征。
DOI：
10.1016/0006-291x(91)90488-s
发表时间：
1991
影响因子：
3.1
作者：
DeNardin,E;Radel,SJ;Genco,RJ
通讯作者：
Genco,RJ
DOI：
10.1146/annurev.bb.13.060184.001203
发表时间：
1984
期刊：
Annual review of biophysics and bioengineering
影响因子：
--
作者：
D. Agard
通讯作者：
D. Agard
影响因子：
5.5
作者：
Makino, A;Prossnitz, ER;Schmid-Schöenbein, GW
通讯作者：
Schmid-Schöenbein, GW
影响因子：
3.4
作者：
de Keijzer, S.;Galloway, J.;Harms, G. S.;Devreotes, P. N.;Iglesias, P. A.
通讯作者：
Iglesias, P. A.