Understanding cellular force transmission dynamics is crucial in mechanobiology. We developed the DNA-based ForceChrono probe to measure force magnitude, duration, and loading rates at the single-molecule level within living cells. The ForceChrono probe circumvents the limitations of single-molecule force spectroscopy by enabling direct measurements within the dynamic cellular environment. Our findings reveal integrin force loading rates of 0.5–2 pN/s and durations ranging from tens of seconds in nascent adhesions to approximately 100 s in mature focal adhesions. The probe’s robust and reversible design allows for continuous monitoring of these dynamic changes as cells undergo morphological transformations. Additionally, by analyzing how mutations, deletions, or pharmacological interventions affect these parameters, we can deduce the functional roles of specific proteins or domains in cellular mechanotransduction. The ForceChrono probe provides detailed insights into the dynamics of mechanical forces, advancing our understanding of cellular mechanics and the molecular mechanisms of mechanotransduction.

中文翻译：

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基于 DNA 的 ForceChrono 探针，用于破译活细胞中的单分子力动力学


了解细胞力传递动力学对于机械生物学至关重要。我们开发了基于 DNA 的 ForceChrono 探针，用于测量活细胞内单分子水平的力大小、持续时间和加载速率。 ForceChrono 探针能够在动态细胞环境中进行直接测量，从而规避了单分子力谱的局限性。我们的研究结果表明，整合素力加载率为 0.5-2 pN/s，持续时间范围从新生粘连的数十秒到成熟粘连的约 100 秒。该探针坚固且可逆的设计允许在细胞经历形态转变时连续监测这些动态变化。此外，通过分析突变、缺失或药物干预如何影响这些参数，我们可以推断特定蛋白质或结构域在细胞力转导中的功能作用。 ForceChrono 探针提供了对机械力动力学的详细见解，增进了我们对细胞力学和力转导分子机制的理解。