Zhou Zhiru, Cui Feiyun, Wen Qi, Susan Zhou H
Department of Chemical Engineering, Worcester Polytechnic Institute, 100 Institute Road, Worcester, Massachusetts 01609, USA.
Department of Physics, Worcester Polytechnic Institute, Worcester, Massachusetts 01609, USA.
Biomicrofluidics. 2021 May 18;15(3):034105. doi: 10.1063/5.0045197. eCollection 2021 May.
Cancer cell migration through tissue pores and tracks into the bloodstream is a critical biological step for cancer metastasis. Although studies have shown that expression of vimentin can induce invasive cell lines, its role in cell cytoskeleton reorganization and cell motility under physical confinement remains unknown. Here, a microfluidic device with cell culture chamber and collagen-coated microchannels was developed as an model for physiological confinement environments. Using this microchannel assay, we demonstrated that the knockdown of vimentin decreases 3T3 fibroblast cell directional migration speed in confined microchannels. Additionally, as cells form dynamic membranes that define the leading edge of motile cells, different leading edge morphologies of 3T3 fibroblast and 3T3 vimentin knockdown cells were observed. The leading edge morphology change under confinement can be explained by the effect of vimentin on cytoskeletal organization and focal adhesion. The microfluidic device integrated with a time-lapse microscope provided a new approach to study the effect of vimentin on cell adhesion, migration, and invasiveness.
癌细胞通过组织孔隙并进入血液循环是癌症转移的关键生物学步骤。尽管研究表明波形蛋白的表达可诱导侵袭性细胞系，但在物理限制条件下其在细胞骨架重组和细胞运动中的作用仍不清楚。在此，开发了一种带有细胞培养室和胶原包被微通道的微流控装置，作为生理限制环境的模型。使用这种微通道检测方法，我们证明了波形蛋白的敲低会降低3T3成纤维细胞在受限微通道中的定向迁移速度。此外，由于细胞形成定义运动细胞前沿的动态膜，观察到了3T3成纤维细胞和3T3波形蛋白敲低细胞不同的前沿形态。限制条件下前沿形态的变化可以通过波形蛋白对细胞骨架组织和粘着斑的作用来解释。与延时显微镜集成的微流控装置为研究波形蛋白对细胞粘附、迁移和侵袭的影响提供了一种新方法。
