Cell tumbling enhances stem cell differentiation in hydrogels via nuclear mechanotransduction

IF 37.2 1区材料科学 Q1 CHEMISTRY, PHYSICAL

Nature Materials Pub Date : 2024-11-01 DOI:10.1038/s41563-024-02038-0

Manish Ayushman, Georgios Mikos, Xinming Tong, Sauradeep Sinha, Eunice Lopez-Fuentes, Sarah Jones, Pamela C. Cai, Hung-Pang Lee, Ashby J. Morrison, Andrew Spakowitz, Sarah C. Heilshorn, Alejandro Sweet-Cordero, Fan Yang

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Abstract

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.

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细胞翻滚通过核机械传导促进干细胞在水凝胶中的分化

细胞可通过扩散、迁移或体积膨胀等全细胞运动，在三维空间中改变其局部生态位。这些行为会持续数小时至数天，影响细胞的长期命运，包括分化。在这里，我们报告了一种在滑动水凝胶中发生的几分钟级的全细胞运动，称为细胞翻滚，其特点是三维细胞动力学和水凝胶变形由几秒到几分钟级的细胞骨架和核活动引起。抑制或促进间充质干细胞翻滚的研究表明，这种行为可促进分化为软骨细胞。此外，细胞翻滚还与全染色质可及性的降低有关，而染色质可及性是增强分化所必需的。细胞翻滚也发生在向其他系的分化过程中，其分化增强效应在各种水凝胶平台中得到了验证。我们的研究结果证实，细胞翻滚是干细胞分化的另一个调节因子，由快速生态位变形和核机械传导介导。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Nature Materials 工程技术-材料科学：综合

CiteScore

62.20

自引率

0.70%

发文量

221

审稿时长

3.2 months

期刊介绍： Nature Materials is a monthly multi-disciplinary journal aimed at bringing together cutting-edge research across the entire spectrum of materials science and engineering. It covers all applied and fundamental aspects of the synthesis/processing, structure/composition, properties, and performance of materials. The journal recognizes that materials research has an increasing impact on classical disciplines such as physics, chemistry, and biology. Additionally, Nature Materials provides a forum for the development of a common identity among materials scientists and encourages interdisciplinary collaboration. It takes an integrated and balanced approach to all areas of materials research, fostering the exchange of ideas between scientists involved in different disciplines. Nature Materials is an invaluable resource for scientists in academia and industry who are active in discovering and developing materials and materials-related concepts. It offers engaging and informative papers of exceptional significance and quality, with the aim of influencing the development of society in the future.