Kinetic model for lamellipodal actin-integrin 'clutch' dynamics
Kinetic model for lamellipodal actin-integrin 'clutch' dynamics
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DOI：
10.4161/cam.2.2.6210
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发表时间：
2008-04-01
影响因子：
3.2
通讯作者：
Lauffenburger, Douglas A.
中科院分区：
文献类型：
--
作者：
Macdonald, Alice;Horwitz, A. Rick;Lauffenburger, Douglas A.
在迁移的细胞中，特别突出的是在细胞前端的片状伪足突起，高度动态的连接形成之间的肌动蛋白细胞骨架和细胞外基质通过连接的整合素粘附受体肌动蛋白丝通过复合物的胞质“连接器”蛋白。肌球蛋白介导的收缩力强烈影响这些粘附复合物的动态行为，显然是以两种相反的方式：消极的细胞产生的力量增强复合物的解离，同时积极的力诱导的信号可以导致加强的连接复合物。从这种动态相互作用产生的净平衡是具有挑战性的，以确定先验，使实验研究难以解释和细胞和/或环境的分子操作难以预测。我们已经建立了一个基于动力学的模型，该系统的动态行为。我们得到的参数值集的范围产生的行为与实验观察到的3 T3细胞和CHO细胞，分别。模型模拟能够产生的结果桩蛋白突变对周转率的肌动蛋白/整联蛋白连接在CHO细胞，这是与最近的文献报道一致。总的来说，尽管当前的模型非常简单，但它为在其上扩展更详细的模型提供了有用的基础。
In migrating cells, with especial prominence in lamellipodial protrusions at the cell front, highly dynamic connections are formed between the actin cytoskeleton and the extracellular matrix through linkages of integrin adhesion receptors to actin filaments via complexes of cytosolic "connector" proteins. Myosin-mediated contractile forces strongly influence the dynamic behavior of these adhesion complexes, apparently in two counter-acting ways: negatively as the cell-generated forces enhance complex dissociation, and at the same time positively as force-induced signaling can lead to strengthening of the linkage complexes. The net balance arising from this dynamic interplay is challenging to ascertain a priori, rendering experimental studies difficult to interpret and molecular manipulations of cell and/or environment difficult to predict. We have constructed a kinetics-based model governing the dynamic behavior of this system. We obtained ranges of parameter value sets yielding behavior consistent with that observed experimentally for 3T3 cells and for CHO cells, respectively. Model simulations are able to produce results for the effects of paxillin mutations on the turnover rate of actin/integrin linkages in CHO cells, which are consistent with recent literature reports. Overall, although this current model is quite simple it provides a useful foundation for more detailed models extending upon it.