Delon Ludivine C, Guo Zhaobin, Kashani Moein Navvab, Yang Chih-Tsung, Prestidge Clive, Thierry Benjamin
Future Industries Institute, University of South Australia, Mawson Lakes, SA 5095, Australia.
ARC Centre of Excellence Convergent Bio-Nano Science and Technology, Australia.
MethodsX. 2020 Jul 2;7:100980. doi: 10.1016/j.mex.2020.100980. eCollection 2020.
This method describes a novel approach to systematically investigate the effect of the fluid shear stress (FSS) on epithelial cells thanks to a single microfluidic device based on Hele-Shaw geometry. The method was validated with intestinal Caco-2 cell monolayers and lung A549 cells. We provide guidelines to adjust the experimental parameters to apply specific ranges of FSS and to specify more accurately the area where to image the cells within the device by the performance of a computational simulation of the fluid flow. Most importantly, this simulation enables to validate the equation. This approach was successfully applied to systematically investigate Caco-2 cell monolayers-based intestine-on-chip models as reported in a companion article published in Biomaterials. This study showed that exposure to microfluidic FSS induces significant phenotypical and functional changes. A detailed understanding of the effects of the FSS will enable the realization of in vitro organs-on-chip models with well-defined characteristics tailored to a specific purpose. The Hele-Shaw approach used in this study could be readily applied to other cell types and adapted for a wide range of physiologically relevant FSS.•Fluid shear stress is a key parameter in the differentiation of epithelial cells cultured in organ-on-chip models.•A simple approach can be used to assess the effect of fluid shear on cellular monolayer cultured in microfluidic devices.•Careful optimization of fluid shear stress environment is necessary for the development of better-defined organ-on-chip models.•Computational simulation of the fluid flow gives an accurate definition of the FSS in a microfluidic channel necessary to interpret the results.
该方法描述了一种新颖的途径，借助基于Hele-Shaw几何形状的单个微流控装置，系统地研究流体剪切应力（FSS）对上皮细胞的影响。该方法已通过肠Caco-2细胞单层和肺A549细胞进行了验证。我们提供了指导方针，以调整实验参数，从而施加特定范围的FSS，并通过流体流动的计算模拟更准确地指定在装置内对细胞进行成像的区域。最重要的是，这种模拟能够验证该方程。如发表在《生物材料》上的一篇配套文章中所报道，这种方法已成功应用于系统地研究基于Caco-2细胞单层的芯片上肠道模型。这项研究表明，暴露于微流控FSS会引起显著的表型和功能变化。对FSS影响的详细了解将有助于实现具有针对特定目的量身定制的明确特征的体外芯片上器官模型。本研究中使用的Hele-Shaw方法可轻松应用于其他细胞类型，并适用于广泛的生理相关FSS。
•流体剪切应力是芯片上器官模型中培养的上皮细胞分化的关键参数。
•可以使用一种简单的方法来评估流体剪切对微流控装置中培养的细胞单层的影响。
•为了开发更明确的芯片上器官模型，仔细优化流体剪切应力环境是必要的。
•流体流动的计算模拟给出了微流控通道中FSS的准确定义，这对于解释结果是必要的。
