Department of Chemical Engineering, Delft University of Technology, Delft, 2629, HZ, The Netherlands.
Department of Bionanoscience, Kavli Institute of Nanoscience, Delft University of Technology, Delft, 2629, HZ, The Netherlands.
Sci Rep. 2024 Aug 28;14(1):20013. doi: 10.1038/s41598-024-70759-y.
Tissue surface tension influences cell sorting and tissue fusion. Earlier mechanical studies suggest that multicellular spheroids actively reinforce their surface tension with applied force. Here we study this open question through high-throughput microfluidic micropipette aspiration measurements on cell spheroids to identify the role of force duration and spheroid deformability. In particular, we aspirate spheroid protrusions of mice fibroblast NIH3T3 and human embryonic HEK293T homogeneous cell spheroids into micron-sized capillaries for different pressures and monitor their viscoelastic creep behavior. We find that larger spheroid deformations lead to faster cellular retraction once the pressure is released, regardless of the applied force. Additionally, less deformable NIH3T3 cell spheroids with an increased expression level of alpha-smooth muscle actin, a cytoskeletal protein upregulating cellular contractility, also demonstrate slower cellular retraction after pressure release for smaller spheroid deformations. Moreover, HEK293T cell spheroids only display cellular retraction at larger pressures with larger spheroid deformations, despite an additional increase in viscosity at these larger pressures. These new insights demonstrate that spheroid viscoelasticity is deformation-dependent and challenge whether surface tension truly reinforces at larger aspiration pressures.
组织表面张力会影响细胞分类和组织融合。早期的力学研究表明，多细胞球体通过施加的力积极增强其表面张力。在这里，我们通过高通量微流控微管吸吮测量对细胞球体进行研究，以确定力持续时间和球体可变形性的作用。具体来说，我们将小鼠成纤维细胞 NIH3T3 和人胚胎 HEK293T 均质细胞球体的球体突起吸入到微米级的毛细管中，施加不同的压力，并监测它们的粘弹性蠕变行为。我们发现，无论施加的力如何，较大的球体变形都会导致压力释放后细胞更快地回缩。此外，表达水平增加的 α-平滑肌肌动蛋白（一种上调细胞收缩性的细胞骨架蛋白）的 NIH3T3 细胞球体，在较小的球体变形后，压力释放后的细胞回缩也更慢。此外，尽管在这些较大的压力下粘度会增加，但 HEK293T 细胞球体仅在较大的压力和较大的球体变形下才显示出细胞回缩。这些新的见解表明，球体的粘弹性是变形依赖性的，并质疑在较大的抽吸压力下表面张力是否真的会增强。
