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通过单粒子运动的超局域定位成像揭示分子识别的瞬态事件。

Revealing transient events of molecular recognition via super-localization imaging of single-particle motion.

机构信息

State Key Laboratory of Analytical Chemistry for Life Science and Collaborative Innovation Center of Chemistry for Life Sciences, School of Chemistry and Chemical Engineering, Nanjing University, 163 Xianlin Road, Nanjing, 210023, P. R. China.

出版信息

Sci Rep. 2019 Mar 19;9(1):4870. doi: 10.1038/s41598-019-41239-5.

DOI:10.1038/s41598-019-41239-5
PMID:30890738
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6424965/
Abstract

Molecular recognition plays an important role in biological systems and relates to a wide range of applications in disease diagnostics and therapeutics. Studies based on steady state or ensemble analysis may mask critical dynamic information of single recognition events. Here we report a study of monitoring the transient molecular recognition via single particle motion. We utilized a super-localization imaging methodology, to comprehensively evaluate the rotational Brownian motion of a single nanoparticle in spatial-temporal-frequential domain, with a spatial accuracy ~20 nm and a temporal resolution of ~10 ms. The transient moment of molecular encountering was captured and different binding modes were discriminated. We observed that the transient recognition events were not static states of on or off, but stochastically undergoes dynamical transformation between different binding modes. This study improves our understanding about the dynamic nature of molecular recognition events beyond the ensemble characterization via binding constant.

摘要

分子识别在生物系统中起着重要作用,与疾病诊断和治疗的广泛应用有关。基于稳态或整体分析的研究可能会掩盖单个识别事件的关键动态信息。在这里,我们报告了通过单个颗粒运动监测瞬时分子识别的研究。我们利用超局部化成像方法,在时空频域中全面评估单个纳米颗粒的旋转布朗运动,空间精度约为 20nm,时间分辨率约为 10ms。捕获了分子相遇的瞬时时刻,并区分了不同的结合模式。我们观察到,瞬态识别事件不是开或关的静态状态,而是在不同的结合模式之间随机经历动态转换。这项研究提高了我们对分子识别事件动态性质的理解,超越了通过结合常数对整体特征的描述。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/51ae/6424965/7865de3b17fb/41598_2019_41239_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/51ae/6424965/3a7d23ebd0c0/41598_2019_41239_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/51ae/6424965/7ffbd0ee6431/41598_2019_41239_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/51ae/6424965/83e50f3186c0/41598_2019_41239_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/51ae/6424965/7865de3b17fb/41598_2019_41239_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/51ae/6424965/3a7d23ebd0c0/41598_2019_41239_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/51ae/6424965/7ffbd0ee6431/41598_2019_41239_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/51ae/6424965/83e50f3186c0/41598_2019_41239_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/51ae/6424965/7865de3b17fb/41598_2019_41239_Fig4_HTML.jpg

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