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.

中文翻译：

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光调谐水凝胶通过机械信号分子的积累揭示了细胞对快速刚度变化的感知


细胞使用牵引力来感知环境中的机械线索。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大的力，但它在解决它们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。在这里，使用具有光响应刚性的水凝胶，我们表明细胞对刚性变化的反应是频率依赖性的。引人注目的是，在某些频率下，细胞牵引力超过静态基材上的牵引力，刚度高出 4 倍，挑战了已建立的分子离合器模型。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它们的积累，从而增强动态环境中的长期细胞牵引。因此，我们提出了一种将即时机械传感与扩展机械信号融合在一起的新模型。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性，强调了考虑即时和长期细胞反应的重要性。