Reactive oxygen species–resistant ultrastable super-resolution DNA framework dots
Abstract
Nanoconfinement as observed in natural (e.g. green fluorescent protein, GFP) or artificial (metal-organic or covalent organic frameworks) systems effectively modulates chemical and physical properties of encapsulated molecules for various photonic, electronic, or catalytic applications. Inspired by GFP’s barrel-like peptide scaffold, which stabilizes the chromophore within a confined space, here we develop photobleaching-resistant super-resolution DNA framework (SDF) dots that enables programmable confinement of various types of fluorophores within the inner cavity resembling GFP. We find that SDF dots are resistant to reactive oxygen species-induced photobleaching due to the shielding effects of DNA frameworks. SDF dots with four fluorophores labeling inside of the cavity leads to ~1.8-fold enhancement in photostability compared to the corner labeling, whereas ~50-fold enhancement compared to single fluorophore labeled on double-stranded DNA. These ultrastable SDF dots are readily adaptable for super-resolution imaging including stimulated emission depletion (STED) and structured illumination microscopy (SIM) imaging. We realize STED imaging of live cell membranes over 30 min. We further construct ultrastable super-resolution SIM barcodes that can distinguish eighteen colored barcodes with a spatial resolution of ~70 nm. This strategy provides a versatile platform for engineering ultrastable fluorescent probes for advancing super-resolution imaging and single-particle tracking in biophysics and biomedical research.
Article Details
Journal Info
Proceedings of the National Academy of Sciences
National Academy of Sciences
Authors (13)
Chengpin Liang
State Key Laboratory of Synergistic Chem-Bio Synthesis, School of Chemistry and Chemical Engineering, New Cornerstone Science Laboratory, Frontiers Science Center for Transformative Molecules and National Center for Translational Medicine, Shanghai Jiao Tong University
Qingting Li
State Key Laboratory of Synergistic Chem-Bio Synthesis, School of Chemistry and Chemical Engineering, New Cornerstone Science Laboratory, Frontiers Science Center for Transformative Molecules and National Center for Translational Medicine, Shanghai Jiao Tong University
Bin Chen
Tingting Zhai
Department of Mechanical Engineering, The University of Hong Kong,Hong Kong (SAR), Pokfulam 999077, China
Xiaoqian Luo
State Key Laboratory of Synergistic Chem-Bio Synthesis, School of Chemistry and Chemical Engineering, New Cornerstone Science Laboratory, Frontiers Science Center for Transformative Molecules and National Center for Translational Medicine, Shanghai Jiao Tong University
Yang Yang
Jiang Qian
State Key Laboratory of Synergistic Chem-Bio Synthesis, School of Chemistry and Chemical Engineering, New Cornerstone Science Laboratory, Frontiers Science Center for Transformative Molecules and National Center for Translational Medicine, Shanghai Jiao Tong University
Dan Zhao
Shihua Luo
Department of Traumatology, Rui Jin Hospital, School of Medicine, Shanghai Jiao Tong University
Fei Wang
Qian Li
Jianlei Shen
State Key Laboratory of Synergistic Chem-Bio Synthesis, School of Chemistry and Chemical Engineering, New Cornerstone Science Laboratory, Frontiers Science Center for Transformative Molecules and National Center for Translational Medicine, Shanghai Jiao Tong University
Chunhai Fan
State Key Laboratory of Synergistic Chem-Bio Synthesis, School of Chemistry and Chemical Engineering, New Cornerstone Science Laboratory, Frontiers Science Center for Transformative Molecules, Zhang Jiang Institute for Advanced Study and National Center for Translational Medicine