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Probing nanoscale self-assembly of nonfluorescent small molecules inside live mammalian cells.


ABSTRACT: Like cellular proteins that form fibrillar nanostructures, small hydrogelator molecules self-assemble in water to generate molecular nanofibers. In contrast to the well-defined (dys)functions of endogenous protein filaments, the fate of intracellular assembly of small molecules remains largely unknown. Here we demonstrate the imaging of enzyme-triggered self-assembly of nonfluorescent small molecules by doping the molecular assemblies with a fluorescent hydrogelator. The cell fractionation experiments, fluorescent imaging, and electron microscopy indicate that the hydrogelators self-assemble and localize to the endoplasmic reticulum (ER) and are likely processed via the cellular secretory pathway (i.e., ER-Golgi-lysosomes/secretion). This work, as the first example of the use of correlative light and electron microscopy for probing the self-assembly of nonfluorescent small molecules inside live mammalian cells, not only establishes a general strategy to provide the spatiotemporal profile of the assemblies of small molecules inside cells but may lead to a new paradigm for regulating cellular functions based on the interactions between the assemblies of small molecules (e.g., molecular nanofibers) and subcellular organelles.

SUBMITTER: Gao Y 

PROVIDER: S-EPMC3845088 | biostudies-other | 2013 Oct

REPOSITORIES: biostudies-other

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Probing nanoscale self-assembly of nonfluorescent small molecules inside live mammalian cells.

Gao Yuan Y   Berciu Cristina C   Kuang Yi Y   Shi Junfeng J   Nicastro Daniela D   Xu Bing B  

ACS nano 20130925 10


Like cellular proteins that form fibrillar nanostructures, small hydrogelator molecules self-assemble in water to generate molecular nanofibers. In contrast to the well-defined (dys)functions of endogenous protein filaments, the fate of intracellular assembly of small molecules remains largely unknown. Here we demonstrate the imaging of enzyme-triggered self-assembly of nonfluorescent small molecules by doping the molecular assemblies with a fluorescent hydrogelator. The cell fractionation exper  ...[more]

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