title: Microfluidic gradient device for studying mesothelial cell migration and the effect of chronic carbon nanotube exposure.
abstract: 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 (0.02μg 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 resemblesin vivocell 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.
authors.affiliation: Lane Department of Computer Science and Electrical Engineering, West Virginia University, Morgantown, WV 26506, USA.
authors.forename: Hanyuan
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Basic Pharmaceutical Sciences, West Virginia University, Morgantown, WV 26506, USA.
authors.forename: Warangkana
authors.initials: W
authors.lastname: Lohcharoenkal
authors.affiliation: Lane Department of Computer Science and Electrical Engineering, West Virginia University, Morgantown, WV 26506, USA.
authors.forename: Jianbo
authors.initials: J
authors.lastname: Sun
authors.affiliation: Lane Department of Computer Science and Electrical Engineering, West Virginia University, Morgantown, WV 26506, USA.
authors.forename: Xiang
authors.initials: X
authors.lastname: Li
authors.affiliation: Pathology and Physiology Research Branch, National Institute for Occupational Safety and Health, Morgantown, WV 26505, USA.
authors.forename: Liying
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Mechanical and Aerospace Engineering, West Virginia University, Morgantown, WV 26506, USA.
authors.forename: Nianqiang
authors.initials: N
authors.lastname: Wu
authors.affiliation: Department of Basic Pharmaceutical Sciences, West Virginia University, Morgantown, WV 26506, USA.
authors.forename: Yon
authors.initials: Y
authors.lastname: Rojanasakul
authors.affiliation: Lane Department of Computer Science and Electrical Engineering, West Virginia University, Morgantown, WV 26506, USA.
authors.forename: Yuxin
authors.initials: Y
authors.lastname: Liu
keywords: cell migration; human pleural mesothelial cells; microfluidics; nanomaterial effects; static gradient device