Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, MO 63110, United States; Department of Mechanical Engineering and Materials Science, Washington University, St. Louis, MO 63130, United States.
Exp Cell Res. 2013 Oct 1;319(16):2490-500. doi: 10.1016/j.yexcr.2013.06.017. Epub 2013 Jul 29.
The dynamic responses of actin stress fibers within a cell's cytoskeleton are central to the development and maintenance of healthy tissues and organs. Disturbances to these underlie a broad range of pathologies. Because of the importance of these responses, extensive experiments have been conducted in vitro to characterize actin cytoskeleton dynamics of cells cultured upon two-dimensional substrata, and the first experiments have been conducted for cells within three-dimensional tissue models. Three mathematical models exist for predicting the dynamic behaviors observed. Surprisingly, despite differing viewpoints on how actin stress fibers are stabilized or destabilized, all of these models are predictive of a broad range of available experimental data. Coarsely, the models of Kaunas and co-workers adopt a strategy whereby mechanical stretch can hasten the depolymerization actin stress fibers that turn over constantly, while the models of Desphande and co-workers adopt a strategy whereby mechanical stress is required to activate the formation of stress fibers and subsequently stabilize them. In three-dimensional culture, elements of both approaches appear necessary to predict observed phenomena, as embodied by the model of Lee et al. After providing a critical review of existing models, we propose lines of experimentation that might be able to test the different principles underlying their kinetic laws.
细胞骨架中的肌动蛋白应力纤维的动态响应是健康组织和器官发育和维持的核心。这些动态响应的紊乱是广泛病理学的基础。由于这些响应的重要性,已经进行了广泛的实验,以表征在二维基质上培养的细胞中的肌动蛋白细胞骨架动力学,并且已经针对三维组织模型中的细胞进行了第一次实验。存在三种用于预测观察到的动态行为的数学模型。令人惊讶的是,尽管对于如何稳定或不稳定肌动蛋白应力纤维存在不同的观点,但所有这些模型都可以预测广泛的可用实验数据。粗略地说,Kaunas 及其同事的模型采用一种策略,即机械拉伸可以加速不断进行解聚的肌动蛋白应力纤维,而 Desphande 及其同事的模型采用一种策略,即需要机械应力来激活应力纤维的形成,随后稳定它们。在三维培养中,这两种方法的要素似乎都需要预测观察到的现象,这体现在 Lee 等人的模型中。在对现有模型进行批判性回顾后,我们提出了可能能够测试其动力学定律背后不同原理的实验方案。