了解细胞力传递动力学在机械生物学中至关重要。我们开发了基于DNA的ForceChrono探针来测量力的大小,持续时间,和单分子水平的负载率在活细胞内。ForceChrono探针通过在动态细胞环境中进行直接测量来规避体外单分子力光谱学的局限性。我们的发现显示整合素的力加载速率为0.5-2pN/s,持续时间从新生粘连的数十秒到成熟粘连的约100s。探针的稳健和可逆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,删除,或药物干预会影响这些参数,我们可以推断特定蛋白质或结构域在细胞机械转导中的功能作用。ForceChrono探测器提供了对机械力动力学的详细见解,提高我们对细胞力学和机械传导的分子机制的理解。
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 in vitro 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.