Endothelial cells undergo morphological, biomechanical, and dynamic changes in response to tumor necrosis factor-α.

Endothelial cells undergo morphological, biomechanical, and dynamic changes in response to tumor necrosis factor-α.
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DOI:
10.1007/s00249-012-0851-3
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发表时间:
2012-11
影响因子:
2
通讯作者:
Aranda-Espinoza, Helim
Aranda-Espinoza, Helim
中科院分区:
生物学4区
文献类型:
--
作者:
Stroka, Kimberly M.;Vaitkus, Janina A.;Aranda-Espinoza, Helim

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免疫反应触发了一系列复杂的事件,其中之一是从单核细胞和巨噬细胞等基质细胞释放细胞因子肿瘤坏死因子-α(肿瘤坏死因子-α)。在这项工作中,我们探索了肿瘤坏死因子-α对内皮细胞(ECs)的生物物理效应,包括细胞形态、生物力学、迁移和细胞骨架动力学的变化。我们发现,肿瘤坏死因子-α诱导了广泛的细胞面积和纵横比的分布,这些特性在治疗过程中平均增加。有趣的是,长宽比在暴露于肿瘤坏死因子-α的10小时左右达到峰值,也对应于施加牵引力的峰值。同时,用肿瘤坏死因子-α处理的内皮细胞软化,我们认为这与估计的细胞体积显著增加有关。此外,我们对迁移动力学的评估表明,在肿瘤坏死因子-α治疗后,细胞长径比与迁移速度呈负相关,提示细胞形状可能是炎症反应过程中EC迁移的重要功能调节因素。最后,我们讨论了在肿瘤坏死因子-α治疗过程中F-肌动蛋白细丝重组的基本机制,并演示了现有肌动蛋白细丝的动态移动。综上所述,我们的结果提示炎症反应过程中内皮细胞的形态、生物力学、迁移和细胞骨架动力学之间存在功能联系。
The immune response triggers a complicated sequence of events, one of which is release of the cytokine tumor necrosis factor-α (TNF-α) from stromal cells such as monocytes and macrophages. In this work we explored the biophysical effects of TNF-α on endothelial cells (ECs), including changes in cell morphology, biomechanics, migration, and cytoskeletal dynamics. We found that TNF-α induces a wide distribution of cell area and aspect ratio, with these properties increasing on average during treatment. Interestingly, aspect ratio peaks around 10 hours of exposure to TNF-α, corresponding also to a peak in exerted traction forces. Meanwhile, ECs treated with TNF-α soften, and we associate this with significant increases in estimated cellular volume. In addition, our evaluation of migratory dynamics demonstrates an inverse correlation between cell aspect ratio and migration speed after TNF-α treatment, suggesting that cell shape may be an important functional regulator of EC migration during an inflammatory response. Finally, we address the basic mechanics of how the reorganization of F-actin filaments occurs during TNF-α treatment, and we demonstrate a dynamic shift of existing actin filaments. Together, our results suggest a functional link between EC morphology, biomechanics, migration, and cytoskeletal dynamics during an inflammatory response.
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