流动下的变形和癌细胞的形态恢复。
Deformation under flow and morphological recovery of cancer cells.
发表日期:2024 Jul 12
作者:
Emile Gasser, Emilie Su, Kotryna Vaidžiulytė, Nassiba Abbade, Hamizah Cognart, Jean-Baptiste Manneville, Jean-Louis Viovy, Matthieu Piel, Jean-Yves Pierga, Kyohei Terao, Catherine Villard
来源:
LAB ON A CHIP
摘要:
转移级联包括从原发肿瘤脱离的细胞的血液循环步骤。当细胞在微脉管系统中循环时,这个阶段涉及显着的剪切应力以及大而快速的变形。这些机械刺激在微流体装置中得到了很好的再现。然而,变形后的恢复动力学对于理解细胞如何穿过单个血液动力学循环中遇到的多个毛细血管收缩也至关重要。这项工作中开发的微流体系统允许在狭窄微通道内压力驱动细胞变形后的无流动条件下研究单细胞恢复。我们使用三种乳腺癌细胞系——即 MCF-7、SK-BR3 和 MDA-MB231——作为代表不同癌症表型的细胞模型。改变收缩的大小可以探索中度至强变形状态,后者与质膜气泡的形成有关。在中等变形状态下,所有细胞类型都表现出快速弹性恢复行为,然后是较慢的粘弹性状态,这可以通过双指数衰减来很好地描述。在这三种细胞类型中,间充质表型的细胞,即 MDA-MB231 细胞,更柔软且最像液体,这与之前的研究一致。我们在这里的主要发现是,我们的新型微流体系统揭示的快速弹性恢复机制受到细胞收缩性的控制,而细胞收缩性由细胞皮层的完整性确保。我们的结果表明,细胞皮层在毛细血管变形后允许循环肿瘤细胞快速形态恢复,从而在循环肿瘤细胞的转运中发挥重要作用。
The metastatic cascade includes a blood circulation step for cells detached from the primary tumor. This stage involves significant shear stress as well as large and fast deformation as the cells circulate through the microvasculature. These mechanical stimuli are well reproduced in microfluidic devices. However, the recovery dynamics after deformation is also pivotal to understand how a cell can pass through the multiple capillary constrictions encountered during a single hemodynamic cycle. The microfluidic system developed in this work allows single cell recovery to be studied under flow-free conditions following pressure-actuated cell deformation inside constricted microchannels. We used three breast cancer cell lines - namely MCF-7, SK-BR3 and MDA-MB231 - as cellular models representative of different cancer phenotypes. Changing the size of the constriction allows exploration of moderate to strong deformation regimes, the latter being associated with the formation of plasma membrane blebs. In the regime of moderate deformation, all cell types display a fast elastic recovery behavior followed by a slower viscoelastic regime, well described by a double exponential decay. Among the three cell types, cells of the mesenchymal phenotype, i.e. the MDA-MB231 cells, are softer and the most fluid-like, in agreement with previous studies. Our main finding here is that the fast elastic recovery regime revealed by our novel microfluidic system is under the control of cell contractility ensured by the integrity of the cell cortex. Our results suggest that the cell cortex plays a major role in the transit of circulating tumor cells by allowing their fast morphological recovery after deformation in blood capillaries.