Photo-tunable hydrogels reveal cellular sensing of rapid rigidity changes through the accumulation of mechanical signaling molecules

IF 19.8 1区 医学 Q1 CELL & TISSUE ENGINEERING
Jiapeng Yang, Peng Wang, Yu Zhang, Man Zhang, Qian Sun, Huiyan Chen, Liang Dong, Zhiqin Chu, Bin Xue, Wouter David Hoff, Changsheng Zhao, Wei Wang, Qiang Wei, Yi Cao
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引用次数: 0

Abstract

Cells use traction forces to sense mechanical cues in their environment. While the molecular clutch model effectively explains how cells exert more forces on stiffer substrates, it falls short in addressing their adaptation to dynamic mechanical fluctuations prevalent in tissues and organs. Here, using hydrogel with photo-responsive rigidity, we show that cells’ response to rigidity changes is frequency dependent. Strikingly, at certain frequencies, cellular traction forces exceed those on static substrates 4-fold stiffer, challenging the established molecular clutch model. We discover that the discrepancy between the rapid adaptation of traction forces and the slower deactivation of mechanotransduction signaling proteins results in their accumulation, thereby enhancing long-term cellular traction in dynamic settings. Consequently, we propose a new model that melds immediate mechanosensing with extended mechanical signaling. Our study underscores the significance of dynamic rigidity in the development of synthetic biomaterials, emphasizing the importance of considering both immediate and prolonged cellular responses.

Abstract Image

光可调水凝胶揭示了细胞通过积累机械信号分子感知快速刚性变化的过程
细胞利用牵引力来感知周围环境中的机械线索。虽然分子离合器模型有效地解释了细胞如何在较硬的基质上施加更多的力,但却无法解释细胞如何适应组织和器官中普遍存在的动态机械波动。在这里,我们利用具有光响应刚性的水凝胶,证明细胞对刚性变化的反应与频率有关。令人震惊的是,在某些频率下,细胞的牵引力超过了静态基质硬度的 4 倍,这对已有的分子离合器模型提出了挑战。我们发现,牵引力的快速适应与机械转导信号蛋白的缓慢失活之间的差异导致了信号蛋白的积累,从而增强了动态环境下细胞的长期牵引力。因此,我们提出了一个将即时机械传感与扩展机械信号传递融为一体的新模型。我们的研究强调了动态刚性在合成生物材料开发中的重要意义,强调了同时考虑即时和长期细胞反应的重要性。
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来源期刊
Cell stem cell
Cell stem cell 生物-细胞生物学
CiteScore
37.10
自引率
2.50%
发文量
151
审稿时长
42 days
期刊介绍: Cell Stem Cell is a comprehensive journal covering the entire spectrum of stem cell biology. It encompasses various topics, including embryonic stem cells, pluripotency, germline stem cells, tissue-specific stem cells, differentiation, epigenetics, genomics, cancer stem cells, stem cell niches, disease models, nuclear transfer technology, bioengineering, drug discovery, in vivo imaging, therapeutic applications, regenerative medicine, clinical insights, research policies, ethical considerations, and technical innovations. The journal welcomes studies from any model system providing insights into stem cell biology, with a focus on human stem cells. It publishes research reports of significant importance, along with review and analysis articles covering diverse aspects of stem cell research.
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