Mapping Intracellular Diffusion Distribution Using Single Quantum Dot Tracking: Compartmentalized Diffusion Defined by Endoplasmic Reticulum

Mapping Intracellular Diffusion Distribution Using Single Quantum Dot Tracking: Compartmentalized Diffusion Defined by Endoplasmic Reticulum
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使用单量子点追踪绘制细胞内扩散分布:内质网定义的区室化扩散

DOI:
10.1021/ja511273c
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发表时间:
2015-01-14
影响因子:
15
通讯作者:
Wang, Peng-Ye
Wang, Peng-Ye
中科院分区:
化学1区
文献类型:
--
作者:
Li, Hui;Dou, Shuo-Xing;Wang, Peng-Ye

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被引文献

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拥挤的细胞内环境影响扩散介导的细胞过程,例如代谢、信号传导和运输。大分子物质在异质细胞质中的扩散受阻现象已被研究多年,但其扩散分布的细节及其起源仍不清楚。在这里,我们介绍了一种新的方法来快速映射单细胞中的扩散分布的基础上单粒子跟踪(SPT)的量子点(QD)。扩散图揭示了异质的细胞内环境,更重要的是,一个未报告的细胞质中的QD扩散区室化。QD运动和绿色荧光蛋白标记的内质网(ER)动力学的同时观察提供了直接的证据表明,区室化的结果从由ER小管定义的微米级域,和ER池形成限制QD进入的核周区域。使用异硫氰酸荧光素-葡聚糖观察到相同的现象,进一步证实了区室化扩散。这些结果揭示了新的光在细胞中的大分子的扩散运动,细胞内扩散分布的映射可用于开发基于纳米颗粒的药物输送和治疗策略。
The crowded intracellular environment influences the diffusion-mediated cellular processes, such as metabolism, signaling, and transport. The hindered diffusion of macromolecules in heterogeneous cytoplasm has been studied over years, but the detailed diffusion distribution and its origin still remain unclear. Here, we introduce a novel method to map rapidly the diffusion distribution in single cells based on single-particle tracking (SPT) of quantum dots (QDs). The diffusion map reveals the heterogeneous intracellular environment and, more importantly, an unreported compartmentalization of QD diffusions in cytoplasm. Simultaneous observations of QD motion and green fluorescent protein-tagged endoplasmic reticulum (ER) dynamics provide direct evidence that the compartmentalization results from micron-scale domains defined by ER tubules, and ER cisternae form perinuclear areas that restrict QDs to enter. The same phenomenon was observed using fluorescein isothiocyanate-dextrans, further confirming the compartmentalized diffusion. These results shed new light on the diffusive movements of macromolecules in the cell, and the mapping of intracellular diffusion distribution may be used to develop strategies for nanoparticle-based drug deliveries and therapeutics.