title: Mapping intracellular diffusion distribution using single quantum dot tracking: compartmentalized diffusion defined by endoplasmic reticulum.
abstract: 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.
authors.affiliation: Key Laboratory of Soft Matter Physics, Beijing National Laboratory for Condensed Matter Physics, Institute of Physics, Chinese Academy of Sciences , Beijing 100190, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.forename: Shuo-Xing
authors.initials: SX
authors.lastname: Dou
authors.forename: Yu-Ru
authors.initials: YR
authors.lastname: Liu
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Ping
authors.initials: P
authors.lastname: Xie
authors.forename: Wei-Chi
authors.initials: WC
authors.lastname: Wang
authors.forename: Peng-Ye
authors.initials: PY
authors.lastname: Wang
mesh_terms: D045744:Cell Line, Tumor; D004058:Diffusion; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D006801:Humans; D045663:Quantum Dots