Department of Biological and Environmental Engineering, Cornell University, Ithaca, NY, USA.
Lab Chip. 2013 Oct 7;13(19):3876-85. doi: 10.1039/c3lc50489a.
This work introduces a contact line pinning based microfluidic platform for the generation of interstitial and intramural flows within a three dimensional (3D) microenvironment for cellular behaviour studies. A contact line pinning method was used to confine a natively derived biomatrix, collagen, in microfluidic channels without walls. By patterning collagen in designated wall-less channels, we demonstrated and validated the intramural flows through a microfluidic channel bounded by a monolayer of endothelial cells (mimic of a vascular vessel), as well as slow interstitial flows within a cell laden collagen matrix using the same microfluidic platform. The contact line pinning method ensured the generation of an engineered endothelial tube with straight walls, and spatially uniform interstitial fluid flows through the cell embedded 3D collagen matrix. Using this device, we demonstrated that the breast tumour cells' (MDA-MB-231 cell line) morphology and motility were modulated by the interstitial flows, and the motility of a sub-population of the cells was enhanced by the presence of the flow. The presented microfluidic platform provides a basic framework for studies of cellular behaviour including cell transmigration, growth, and adhesion under well controlled interstitial and intramural flows, and within a physiologically realistic 3D co-culture setting.
这项工作介绍了一种基于接触线固定的微流控平台,用于在三维(3D)微环境中产生细胞行为研究中的间质和壁内流动。采用接触线固定方法将天然衍生的生物基质胶原限制在无微通道中而无需壁。通过在无壁通道中对胶原进行图案化,我们展示并验证了通过由单层内皮细胞(模拟血管)限定的微流通道的壁内流动,以及使用相同的微流控平台在细胞负载的胶原基质内的缓慢间质流动。接触线固定方法确保了具有直壁的工程化内皮管的生成,以及通过细胞嵌入的 3D 胶原基质的空间均匀间质流体流动。使用该装置,我们证明了间质流动调节了乳腺癌细胞(MDA-MB-231 细胞系)的形态和迁移性,并且流动的存在增强了细胞亚群的迁移性。所提出的微流控平台为细胞行为研究提供了基本框架,包括在良好控制的间质和壁内流动以及生理上逼真的 3D 共培养环境下的细胞迁移、生长和粘附。