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

Yuan Gao, Cristina Berciu, Yi Kuang, Junfeng Shi, Daniela Nicastro, Bing Xu

Research output: Contribution to journalArticle

49 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)9055-9063
Number of pages9
JournalACS Nano
Volume7
Issue number10
DOIs
StatePublished - Oct 22 2013

Keywords

  • enzyme
  • intracellular
  • localization
  • nanofibers
  • self-assembly
  • small molecule

ASJC Scopus subject areas

  • Materials Science(all)
  • Engineering(all)
  • Physics and Astronomy(all)

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