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光学纳米腔中的亚微秒级构象动力学

Sub-microsecond conformational dynamics in an optical nanocavity

Heehun Sung, Sam C Scholten, Pavlina Sasheva, Igor Marinkovic, Warwick P Bowen

arXiv 2607.15925首次发表:更新:

AI 中文总结

研究利用光纤集成硅光子传感器,结合远亚波长光场限制与高光场均匀性抑制蛋白质布朗运动,以亚微秒速度连续单次测量解析蛋白质动力学,揭示隐藏在系综平均中的特性,为理解蛋白质功能开辟新途径。

AI 中文摘要

微秒级构象变化是许多蛋白质功能的基础,但此前需进行系综平均才能在无标记情况下观察到这些变化。对单个蛋白质的单次测量速度不足,且蛋白质布朗运动会掩盖信号。在此,我们报道了一种光纤集成硅光子传感器,它克服了这些障碍,能在连续单次测量中以亚微秒速度解析蛋白质动力学,测量可持续数分钟。这是通过将远亚波长光场限制与高光场均匀性相结合实现的,可将蛋白质布朗运动抑制60倍。在对铁蛋白分子的单次测量中,我们观察到数万个与铁蛋白壳构象波动一致的转变,能在短至400纳秒的时间尺度上解析它们。长时间连续监测转变的能力揭示了隐藏在系综平均中的开关动力学、记忆效应和分子异质性。这为改进对蛋白质功能的机理理解开辟了新途径。

英文摘要

Microsecond conformational changes underlie many protein functions, but ensemble averaging has been needed to observe them without labels. Single-shot measurements on individual proteins have had insufficient speed, while protein Brownian-motion has obscured signals. Here, we report a fibre-integrated silicon-photonic sensor that overcomes these barriers, resolving protein dynamics at sub-microsecond speeds in continuous single-shot measurements that can extend over minutes. This is achieved by combining far-sub-wavelength optical field confinement with high optical field uniformity that suppresses protein Brownian-motion by a factor of sixty. In single-shot measurements on ferritin molecules, we observe tens of thousands of transitions consistent with conformational fluctuations of the ferritin shell, resolving them over timescales as short as 400 ns. The ability to continuously monitor transitions over long times reveals switching kinetics, memory effects and molecular heterogeneity hidden in ensemble averages. This opens a new path to improved mechanistic understanding of protein function.

CommentsMain text, 11 pages, 4 figures; Supplementary Information, 40 pages, 22 figures

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