A Molecular Logic Gate Enables Super-Resolved Imaging of Intracellular Lipid Droplets

10 September 2019, Version 1
This content is a preprint and has not undergone peer review at the time of posting.

Abstract

Photoactivatable dyes enable single-molecule imaging in biology. Despite progress in the development of new fluorophores and labeling strategies, many cellular compartments remain difficult to image beyond the limit of diffraction in living cells. For example, lipid droplets, which are organelles that contain mostly neutral lipids, have eluded single-molecule imaging. To visualize these challenging subcellular targets, it is necessary to develop new fluorescent molecular devices beyond simple on/off switches. Here, we report a fluorogenic molecular logic gate that can be used to image single molecules associated with lipid droplets with excellent specificity. This probe requires the subsequent action of light, a lipophilic environment and a competent nucleophile to produce a fluorescent product. The combination of these requirements results in a probe that can be used to image the boundary of lipid droplets in three dimensions with resolutions beyond the limit of diffraction. Moreover, this probe enables single-molecule tracking of lipids within and between droplets in living cells.

Keywords

Single-molecule localization microscopy
photoactivatable probe
Wolff rearrangement
lipid droplets
single-molecule tracking

Supplementary materials

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Title
Eordogh-chemRxiv2019-SI
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