Keratinocytes are mechanoresponsive to the microflow-induced shear stress
Keratinocytes are mechanoresponsive to the microflow-induced shear stress
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DOI：
10.1002/cm.21521
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发表时间：
2019-02-01
期刊：
影响因子：
2.9
通讯作者：
Banerjee, Indranil
中科院分区：
文献类型：
--
作者：
Agarwal, Tarun;Narayana, Gautham H.;Banerjee, Indranil
在这里，我们报道角质形成细胞在集体和个体细胞水平上对微流诱导的剪切应力做出反应。使用微流体设置，我们明确表明，0.06 达因/厘米 (2) 的低剪切应力可以诱导角质形成细胞的形态变化和细胞骨架重组，而较高的剪切应力 (6 达因/厘米 (2)) 会导致细胞破坏。使用一系列针对不同机械传感器的阻断剂分子，我们证明了肌动蛋白网络在与肌球蛋白和脂筏结合的角质形成细胞机械反应中的关键作用。流动诱导的剪切应力还导致 E-钙粘蛋白和闭锁小带-1 (ZO-1) 表达水平显着升高。我们进一步表明，在剪切应力的影响下，E-钙粘蛋白和 ZO-1 的共定位程度更多地位于细胞-细胞连接处，这表明上皮表型有所改善。在剪切的细胞中还观察到核纤层蛋白表达的增加，这表明机械信号传递到细胞核。预计这项研究可能会在表皮的基础和应用器官发生中找到应用。
Here, we have reported that keratinocytes respond to the microflow-induced shear stress both at the collective and individual cell level. Using a microfluidic setup, we categorically showed that low shear stress of magnitude 0.06 dyne/cm(2) could induce morphological variation and cytoskeletal reorganization in keratinocyte, whereas higher shear stress (6 dyne/cm(2)) resulted in cellular disruption. Using a series of blocker molecules specific to different mechanotransducers, we demonstrated the pivotal role of actin network in keratinocyte mechanoresponsiveness in conjugation with myosin and lipid rafts. Flow-induced shear stress also induced significant elevation in E-cadherin and Zonula occludens-1 (ZO-1) expression levels. We further showed that under the influence of shear stress, the extent of colocalization of E-cadherin and ZO-1 was more at the cell-cell junction that indicates an improvement in the epithelial phenotype. An increase in the expression of nuclear lamin was also observed in the sheared cells that suggest the transmission of mechanical signals to the nucleus. It is envisioned that this study may find its application in basic and applied organogenesis of the epidermis.