Abstract:
:Bright, photostable, and nontoxic fluorescent contrast agents are critical for biological imaging. "Self-healing" dyes, in which triplet states are intramolecularly quenched, enable fluorescence imaging by increasing fluorophore brightness and longevity, while simultaneously reducing the generation of reactive oxygen species that promote phototoxicity. Here, we systematically examine the self-healing mechanism in cyanine-class organic fluorophores spanning the visible spectrum. We show that the Baird aromatic triplet-state energy of cyclooctatetraene can be physically altered to achieve order of magnitude enhancements in fluorophore brightness and signal-to-noise ratio in both the presence and absence of oxygen. We leverage these advances to achieve direct measurements of large-scale conformational dynamics within single molecules at submillisecond resolution using wide-field illumination and camera-based detection methods. These findings demonstrate the capacity to image functionally relevant conformational processes in biological systems in the kilohertz regime at physiological oxygen concentrations and shed important light on the multivariate parameters critical to self-healing organic fluorophore design.
journal_name
Proc Natl Acad Sci U S Aauthors
Pati AK,El Bakouri O,Jockusch S,Zhou Z,Altman RB,Fitzgerald GA,Asher WB,Terry DS,Borgia A,Holsey MD,Batchelder JE,Abeywickrama C,Huddle B,Rufa D,Javitch JA,Ottosson H,Blanchard SCdoi
10.1073/pnas.2006517117subject
Has Abstractpub_date
2020-09-29 00:00:00pages
24305-24315issue
39eissn
0027-8424issn
1091-6490pii
2006517117journal_volume
117pub_type
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