A Carbon Nanotube Optical Reporter Maps Endolysosomal Lipid Flux.

Details

Serval ID
serval:BIB_1B6139F6FBC4
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
A Carbon Nanotube Optical Reporter Maps Endolysosomal Lipid Flux.
Journal
ACS nano
Author(s)
Jena P.V., Roxbury D., Galassi T.V., Akkari L., Horoszko C.P., Iaea D.B., Budhathoki-Uprety J., Pipalia N., Haka A.S., Harvey J.D., Mittal J., Maxfield F.R., Joyce J.A., Heller D.A.
ISSN
1936-086X (Electronic)
ISSN-L
1936-0851
Publication state
Published
Issued date
28/11/2017
Peer-reviewed
Oui
Volume
11
Number
11
Pages
10689-10703
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
Lipid accumulation within the lumen of endolysosomal vesicles is observed in various pathologies including atherosclerosis, liver disease, neurological disorders, lysosomal storage disorders, and cancer. Current methods cannot measure lipid flux specifically within the lysosomal lumen of live cells. We developed an optical reporter, composed of a photoluminescent carbon nanotube of a single chirality, that responds to lipid accumulation via modulation of the nanotube's optical band gap. The engineered nanomaterial, composed of short, single-stranded DNA and a single nanotube chirality, localizes exclusively to the lumen of endolysosomal organelles without adversely affecting cell viability or proliferation or organelle morphology, integrity, or function. The emission wavelength of the reporter can be spatially resolved from within the endolysosomal lumen to generate quantitative maps of lipid content in live cells. Endolysosomal lipid accumulation in cell lines, an example of drug-induced phospholipidosis, was observed for multiple drugs in macrophages, and measurements of patient-derived Niemann-Pick type C fibroblasts identified lipid accumulation and phenotypic reversal of this lysosomal storage disease. Single-cell measurements using the reporter discerned subcellular differences in equilibrium lipid content, illuminating significant intracellular heterogeneity among endolysosomal organelles of differentiating bone-marrow-derived monocytes. Single-cell kinetics of lipoprotein-derived cholesterol accumulation within macrophages revealed rates that differed among cells by an order of magnitude. This carbon nanotube optical reporter of endolysosomal lipid content in live cells confers additional capabilities for drug development processes and the investigation of lipid-linked diseases.

Keywords
hyperspectral microscopy, live-cell imaging, near-infrared fluorescence, single-cell sensing, single-walled carbon nanotubes
Pubmed
Web of science
Open Access
Yes
Create date
25/09/2017 10:32
Last modification date
20/08/2019 13:52
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