Using Polyacrylamide Hydrogels to Model Physiological Aortic Stiffness Reveals that Microtubules Are Critical Regulators of Isolated Smooth Muscle Cell Morphology and Contractility.
Using Polyacrylamide Hydrogels to Model Physiological Aortic Stiffness Reveals that Microtubules Are Critical Regulators of Isolated Smooth Muscle Cell Morphology and Contractility.
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使用聚丙烯酰胺水凝胶对生理主动脉僵硬进行建模表明，微管是分离的平滑肌细胞形态和收缩力的关键调节剂。
DOI：
10.3389/fphar.2022.836710
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发表时间：
2022
影响因子：
5.6
通讯作者：
Warren DT
中科院分区：
文献类型：
--
作者：
Ahmed S;Johnson RT;Solanki R;Afewerki T;Wostear F;Warren DT
血管平滑肌细胞（VSMC）是主动脉壁中层的主要细胞类型，通常以静止、收缩表型存在，其中肌动球蛋白衍生的收缩力维持血管张力。然而，VSMC不是终末分化的，并且可以去分化成增殖的合成表型。肌动球蛋白力的产生对于两种表型的功能都是必不可少的。虽然已经知道了很多关于VSMC肌动球蛋白力产生的机制，现有的测定方法要么是低通量和耗时的，要么是定性的和不一致的。在这项研究中，我们使用聚丙烯酰胺水凝胶，调整到模拟主动脉壁的生理刚度，在VSMC收缩试验。用收缩激动剂血管紧张素II或卡巴胆碱刺激后，孤立的VSMC面积减少。重要的是，血管紧张素II诱导的细胞面积减少与牵引应力产生的增加相关。使用blebbistatin或Y-27632抑制肌动球蛋白活性防止血管紧张素II介导的VSMC形态变化，表明VSMC形态和肌动球蛋白活性的变化是收缩反应的核心组成部分。此外，我们表明，微管的稳定性是一个重要的调节隔离VSMC收缩。无论是秋水仙碱或紫杉醇治疗解耦的血管紧张素II刺激VSMCs的形态和/或牵引应激反应。我们的研究结果支持细胞力学的张力整体模型，我们证明，微管的行为，以平衡肌动球蛋白衍生的牵引应力的产生和调节VSMCs的形态反应。
Vascular smooth muscle cells (VSMCs) are the predominant cell type in the medial layer of the aortic wall and normally exist in a quiescent, contractile phenotype where actomyosin-derived contractile forces maintain vascular tone. However, VSMCs are not terminally differentiated and can dedifferentiate into a proliferative, synthetic phenotype. Actomyosin force generation is essential for the function of both phenotypes. Whilst much is already known about the mechanisms of VSMC actomyosin force generation, existing assays are either low throughput and time consuming, or qualitative and inconsistent. In this study, we use polyacrylamide hydrogels, tuned to mimic the physiological stiffness of the aortic wall, in a VSMC contractility assay. Isolated VSMC area decreases following stimulation with the contractile agonists angiotensin II or carbachol. Importantly, the angiotensin II induced reduction in cell area correlated with increased traction stress generation. Inhibition of actomyosin activity using blebbistatin or Y-27632 prevented angiotensin II mediated changes in VSMC morphology, suggesting that changes in VSMC morphology and actomyosin activity are core components of the contractile response. Furthermore, we show that microtubule stability is an essential regulator of isolated VSMC contractility. Treatment with either colchicine or paclitaxel uncoupled the morphological and/or traction stress responses of angiotensin II stimulated VSMCs. Our findings support the tensegrity model of cellular mechanics and we demonstrate that microtubules act to balance actomyosin-derived traction stress generation and regulate the morphological responses of VSMCs.
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影响因子：
20.1
作者：
Li, SH;Sims, S;Pickering, JG
通讯作者：
Pickering, JG
影响因子：
10.8
作者：
Holle AW;Young JL;Van Vliet KJ;Kamm RD;Discher D;Janmey P;Spatz JP;Saif T
通讯作者：
Saif T
影响因子：
41.2
作者：
Bartolak-Suki, Erzsebet;Imsirovic, Jasmin;Suki, Bela
通讯作者：
Suki, Bela
影响因子：
7.7
作者：
Atkinson SJ;Gontarczyk AM;Alghamdi AA;Ellison TS;Johnson RT;Fowler WJ;Kirkup BM;Silva BC;Harry BE;Schneider JG;Weilbaecher KN;Mogensen MM;Bass MD;Parsons M;Edwards DR;Robinson SD
通讯作者：
Robinson SD
影响因子：
16.6
作者：
Joo, E. Emily;Yamada, Kenneth M.
通讯作者：
Yamada, Kenneth M.