Stretch-induced stress fiber remodeling and the activations of JNK and ERK depend on mechanical strain rate, but not FAK.
Stretch-induced stress fiber remodeling and the activations of JNK and ERK depend on mechanical strain rate, but not FAK.
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DOI：
10.1371/journal.pone.0012470
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发表时间：
2010-08-30
期刊：
影响因子：
3.7
通讯作者：
Kaunas R
中科院分区：
文献类型：
--
作者：
Hsu HJ;Lee CF;Locke A;Vanderzyl SQ;Kaunas R
组织内的细胞受到细胞外基质变形引起的机械力的作用。细胞通过调整肌动蛋白应激纤维的方向和激活细胞内信号蛋白，包括粘着斑激酶(FAK)和丝裂原激活蛋白激酶(MAPKs)来感知和动态响应基质的拉伸。理论分析预测，应力纤维可以松弛拉伸扰动，这取决于基质的应变率。因此，我们假设应力纤维组织和MAPK活性在一定程度上取决于拉伸频率。将表达GFP-肌动蛋白的牛主动脉内皮细胞和人骨肉瘤细胞培养在弹性膜上，并进行不同形式的拉伸。循环拉伸导致应力纤维排列、细胞收缩以及MAPKs JNK、ERK和p38磷酸化的应变率依赖性增加。应变速率的瞬时阶跃变化导致JNK和ERK磷酸化水平的比例瞬时变化，而不影响应力纤维组织。用细胞松弛素D或Y27632阻断应激纤维的收缩功能可降低JNK和ERK的磷酸化水平。先前的研究表明，FAK是拉伸诱导的细胞排列和MAPK激活所必需的。然而，在FAK缺失和表达FAK的小鼠胚胎成纤维细胞中，循环单轴拉伸诱导应力纤维排列和JNK、ERK和p38的磷酸化达到类似的水平。这些结果表明，周期性拉伸诱导的应力纤维排列、细胞收缩和MAPK激活是纤维应变扰动的结果。因此，这些发现揭示了应力纤维松弛和重组在动态力学环境中维持张力动态平衡中的作用。
Cells within tissues are subjected to mechanical forces caused by extracellular matrix deformation. Cells sense and dynamically respond to stretching of the matrix by reorienting their actin stress fibers and by activating intracellular signaling proteins, including focal adhesion kinase (FAK) and the mitogen-activated proteins kinases (MAPKs). Theoretical analyses predict that stress fibers can relax perturbations in tension depending on the rate of matrix strain. Thus, we hypothesized stress fiber organization and MAPK activities are altered to an extent dependent on stretch frequency. Bovine aortic endothelial cells and human osteosarcoma cells expressing GFP-actin were cultured on elastic membranes and subjected to various patterns of stretch. Cyclic stretching resulted in strain rate-dependent increases in stress fiber alignment, cell retraction, and the phosphorylation of the MAPKs JNK, ERK and p38. Transient step changes in strain rate caused proportional transient changes in the levels of JNK and ERK phosphorylations without affecting stress fiber organization. Disrupting stress fiber contractile function with cytochalasin D or Y27632 decreased the levels of JNK and ERK phosphorylation. Previous studies indicate that FAK is required for stretch-induced cell alignment and MAPK activations. However, cyclic uniaxial stretching induced stress fiber alignment and the phosphorylation of JNK, ERK and p38 to comparable levels in FAK-null and FAK-expressing mouse embryonic fibroblasts. These results indicate that cyclic stretch-induced stress fiber alignment, cell retraction, and MAPK activations occur as a consequence of perturbations in fiber strain. These findings thus shed new light into the roles of stress fiber relaxation and reorganization in maintenance of tensional homeostasis in a dynamic mechanical environment.
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