Cell migration is one of the crucial steps in many physiological and pathological processes, including cancer development. Our recent studies have shown that carbon nanotubes (CNTs), similarly to asbestos, can induce accelerated cell growth and invasiveness that contribute to their mesothelioma pathogenicity. Malignant mesothelioma is a very aggressive tumor that develops from cells of the mesothelium, and is most commonly caused by exposure to asbestos. CNTs have a similar structure and mode of exposure to asbestos. This has raised a concern regarding the potential carcinogenicity of CNTs, especially in the pleural area which is a key target for asbestos-related diseases. In this paper, a static microfluidic gradient device was applied to study the migration of human pleural mesothelial cells which had been through a long-term exposure (4 months) to subcytotoxic concentration (0.02 μg cm-2) of single-walled CNTs (SWCNTs). Multiple migration signatures of these cells were investigated using the microfluidic gradient device for the first time. During the migration study, we observed that cell morphologies changed from flattened shapes to spindle shapes prior to their migration after their sensing of the chemical gradient. The migration of chronically SWCNT-exposed mesothelial cells was evaluated under different fetal bovine serum (FBS) concentration gradients, and the migration speeds and number of migrating cells were extracted and compared. The results showed that chronically SWCNT-exposed mesothelial cells are more sensitive to the gradient compared to non-SWCNT-exposed cells. The method described here allows simultaneous detection of cell morphology and migration under chemical gradient conditions, and also allows for real-time monitoring of cell motility that resembles in vivo cell migration. This platform would be much needed for supporting the development of more physiologically relevant cell models for better assessment and characterization of the mesothelioma hazard posed by nanomaterials.

中文翻译：

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用于研究间皮细胞迁移和慢性碳纳米管暴露影响的微流体梯度装置

细胞迁移是许多生理和病理过程（包括癌症发展）的关键步骤之一。我们最近的研究表明，碳纳米管（CNT）与石棉类似，可以诱导加速细胞生长和侵袭，从而导致其间皮瘤致病性。恶性间皮瘤是一种非常具有侵袭性的肿瘤，由间皮细胞发展而来，最常见的是由接触石棉引起的。碳纳米管具有类似的结构和接触石棉的方式。这引起了人们对碳纳米管潜在致癌性的担忧，特别是在胸膜区域，该区域是石棉相关疾病的关键目标。本文采用静态微流控梯度装置研究了长期暴露(4个月)亚细胞毒性浓度(0.02 μg cm-2)的单壁碳纳米管(SWCNTs)后人胸膜间皮细胞的迁移情况。 ）。首次使用微流体梯度装置研究了这些细胞的多重迁移特征。在迁移研究过程中，我们观察到细胞形态在感知化学梯度后迁移前从扁平形状变为纺锤形状。评估长期暴露于SWCNT的间皮细胞在不同胎牛血清（FBS）浓度梯度下的迁移情况，提取并比较迁移速度和迁移细胞数量。结果表明，与未暴露于单壁碳纳米管的细胞相比，长期暴露于单壁碳纳米管的间皮细胞对梯度更敏感。这里描述的方法允许在化学梯度条件下同时检测细胞形态和迁移，并且还允许实时监测类似于体内细胞迁移的细胞运动。非常需要该平台来支持开发更多生理相关的细胞模型，以便更好地评估和表征纳米材料造成的间皮瘤危害。