Uttayarat P, Chen M, Li M, Allen F D, Composto R J, Lelkes P I
Department of Materials Science and Engineering, University of Pennsylvania, USA.
Am J Physiol Heart Circ Physiol. 2008 Feb;294(2):H1027-35. doi: 10.1152/ajpheart.00816.2007. Epub 2007 Dec 21.
The migration of vascular endothelial cells under flow can be modulated by the addition of chemical or mechanical stimuli. The aim of this study was to investigate how topographic cues derived from a substrate containing three-dimensional microtopography interact with fluid shear stress in directing endothelial cell migration. Subconfluent bovine aortic endothelial cells were seeded on fibronectin-coated poly(dimethylsiloxane) substrates patterned with a combinatorial array of parallel and orthogonal microgrooves ranging from 2 to 5 microm in width at a constant depth of 1 microm. During a 4-h time-lapse observation in the absence of flow, the majority of the prealigned cells migrated parallel to the grooves with the distribution of their focal adhesions (FAs) depending on the groove width. No change in this migratory pattern was observed after the cells were exposed to moderate shear stress (13.5 dyn/cm(2)), irrespective of groove direction with respect to flow. After 4-h exposure to high shear stress (58 dyn/cm(2)) parallel to the grooves, the cells continued to migrate in the direction of both grooves and flow. By contrast, when microgrooves were oriented perpendicular to flow, most cells migrated orthogonal to the grooves and downstream with flow. Despite the change in the migration direction of the cells under high shear stress, most FAs and actin microfilaments maintained their original alignment parallel to the grooves, suggesting that topographic cues were more effective than those derived from shear stress in guiding the orientation of cytoskeletal and adhesion proteins during the initial exposure to flow.
流动状态下血管内皮细胞的迁移可通过添加化学或机械刺激来调节。本研究的目的是探究源自含有三维微观形貌的基质的拓扑线索如何与流体剪切应力相互作用，以引导内皮细胞迁移。将亚汇合的牛主动脉内皮细胞接种在涂有纤连蛋白的聚二甲基硅氧烷基质上，该基质具有宽度为2至5微米、深度恒定为1微米的平行和正交微槽组合阵列。在无流动的4小时延时观察期间，大多数预先排列的细胞平行于微槽迁移，其粘着斑（FAs）的分布取决于微槽宽度。在细胞暴露于中等剪切应力（13.5达因/平方厘米）后，无论微槽相对于流动的方向如何，这种迁移模式均未观察到变化。在与微槽平行的高剪切应力（58达因/平方厘米）下暴露4小时后，细胞继续沿微槽和流动方向迁移。相比之下，当微槽垂直于流动方向时，大多数细胞垂直于微槽并随流动向下游迁移。尽管在高剪切应力下细胞迁移方向发生了变化，但大多数粘着斑和肌动蛋白微丝仍保持其与微槽平行的原始排列，这表明在最初暴露于流动时，拓扑线索在引导细胞骨架和粘附蛋白的取向方面比剪切应力衍生的线索更有效。
