南京大学曹毅等近期取得重要工作进展。他们通过研究光响应水凝胶揭示，细胞通过积累机械信号分子感知快速刚性变化的过程。相关研究成果2024年10月21日在线发表于《细胞—干细胞》杂志上。

据介绍，细胞利用牵引力来感知环境中的机械信号。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，但它在解决细胞对组织和器官中普遍存在的，动态机械波动的适应方面存在不足。

使用具有光响应刚性的水凝胶，研究人员表明细胞对刚性变化的反应是频率依赖性的。在某些频率下，细胞牵引力超过了静态基质上的4倍，对已建立的分子离合器模型提出了挑战。研究人员发现，牵引力的快速适应和机械转导信号蛋白的缓慢失活之间的差异，导致了它们的积累，从而在动态环境中增强了长期的细胞牵引力。因此，研究人员提出了一种，将即时机械感应与扩展机械信号融合的新模型。

总之，这一研究强调了动态刚性在合成生物材料开发中的重要性，强调了考虑即时和长期细胞反应的重要性。

附：英文原文

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

Author: 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

Issue&Volume: 2024-10-21

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.

DOI: 10.1016/j.stem.2024.09.016

Source: https://www.cell.com/cell-stem-cell/abstract/S1934-5909(24)00359-X