Malboubi Majid, Jayo Asier, Parsons Maddy, Charras Guillaume
London Centre for Nanotechnology, University College London, UK.
Randall Division of Cell and Molecular Biophysics, Kings College London, UK.
Microelectron Eng. 2015 Aug 16;144:42-45. doi: 10.1016/j.mee.2015.02.022.
During metastasis, cancerous cells leave the primary tumour, pass into the circulatory system, and invade into new tissues. To migrate through the wide variety of environments they encounter, the cells must be able to remodel their cell shape efficiently to squeeze through small gaps in the extracellular matrix or extravasate into the blood stream or lymphatic system. Several studies have shown that the nucleus is the main limiting factor to migration through small gaps (Wolf et al., 2013; Harada et al., 2014; Mak et al., 2013). To understand the physical limits of cancer cell translocation in confined environments, we have fabricated a microfluidic device to study their ability to adapt their nuclear and cellular shape when passing through small gaps. The device is open access for ease of use and enables examination of the effect of different levels of spatial confinement on cell behaviour and morphology simultaneously. The results show that increasing cell confinement decreases the ability of cells to translocate into small gaps and that cells cannot penetrate into the microchannels below a threshold cross-section.
在转移过程中，癌细胞离开原发肿瘤，进入循环系统，并侵入新的组织。为了在它们遇到的各种各样的环境中迁移，细胞必须能够有效地重塑其细胞形状，以便挤过细胞外基质中的小间隙，或者渗出到血流或淋巴系统中。多项研究表明，细胞核是细胞通过小间隙迁移的主要限制因素（Wolf等人，2013年；Harada等人，2014年；Mak等人，2013年）。为了了解癌细胞在受限环境中迁移的物理极限，我们制作了一种微流控装置，以研究它们在通过小间隙时调整细胞核和细胞形状的能力。该装置易于使用且开放获取，能够同时检测不同程度的空间限制对细胞行为和形态的影响。结果表明，增加细胞限制会降低细胞迁移到小间隙中的能力，并且细胞无法穿透低于阈值横截面的微通道。
