Ayushman Manish, Mikos Georgios, Tong Xinming, Sinha Sauradeep, Lopez-Fuentes Eunice, Jones Sarah, Cai Pamela C, Lee Hung-Pang, Morrison Ashby J, Spakowitz Andrew, Heilshorn Sarah C, Sweet-Cordero Alejandro, Yang Fan
Department of Bioengineering, Stanford University, Stanford, CA, USA.
Department of Chemical Engineering, Stanford University, Stanford, CA, USA.
Nat Mater. 2025 Feb;24(2):312-322. doi: 10.1038/s41563-024-02038-0. Epub 2024 Nov 1.
Cells can deform their local niche in three dimensions via whole-cell movements such as spreading, migration or volume expansion. These behaviours, occurring over hours to days, influence long-term cell fates including differentiation. Here we report a whole-cell movement that occurs in sliding hydrogels at the minutes timescale, termed cell tumbling, characterized by three-dimensional cell dynamics and hydrogel deformation elicited by heightened seconds-to-minutes-scale cytoskeletal and nuclear activity. Studies inhibiting or promoting the cell tumbling of mesenchymal stem cells show that this behaviour enhances differentiation into chondrocytes. Further, it is associated with a decrease in global chromatin accessibility, which is required for enhanced differentiation. Cell tumbling also occurs during differentiation into other lineages and its differentiation-enhancing effects are validated in various hydrogel platforms. Our results establish that cell tumbling is an additional regulator of stem cell differentiation, mediated by rapid niche deformation and nuclear mechanotransduction.
细胞可通过诸如铺展、迁移或体积膨胀等全细胞运动在三维空间中改变其局部微环境。这些行为在数小时至数天内发生，会影响包括分化在内的长期细胞命运。在此，我们报告一种在滑动水凝胶中以分钟为时间尺度发生的全细胞运动，称为细胞翻滚，其特征在于由秒到分钟尺度的细胞骨架和核活动增强引发的三维细胞动力学和水凝胶变形。抑制或促进间充质干细胞细胞翻滚的研究表明，这种行为可增强向软骨细胞的分化。此外，它与整体染色质可及性的降低有关，而这是增强分化所必需的。细胞翻滚在向其他谱系的分化过程中也会发生，并且其增强分化的作用在各种水凝胶平台中得到了验证。我们的结果表明，细胞翻滚是干细胞分化的另一种调节因子，由快速的微环境变形和核机械转导介导。
