Abstract

Endosomes, lysosomes and related catabolic organelles are a dynamic continuum of vacuolar structures that impact a number of cell physiological processes such as protein/lipid metabolism, nutrient sensing and cell survival. Here we develop a library of ultra-pH-sensitive fluorescent nanoparticles with chemical properties that allow fine-scale, multiplexed, spatio-temporal perturbation and quantification of catabolic organelle maturation at single organelle resolution to support quantitative investigation of these processes in living cells. Deployment in cells allows quantification of the proton accumulation rate in endosomes; illumination of previously unrecognized regulatory mechanisms coupling pH transitions to endosomal coat protein exchange; discovery of distinct pH thresholds required for mTORC1 activation by free amino acids versus proteins; broad-scale characterization of the consequence of endosomal pH transitions on cellular metabolomic profiles; and functionalization of a context-specific metabolic vulnerability in lung cancer cells. Together, these biological applications indicate the robustness and adaptability of this nanotechnology-enabled â detection and perturbation ' strategy.

Original languageEnglish (US)
Article number8524
JournalNature Communications
Volume6
DOIs
StatePublished - Oct 5 2015

Fingerprint

organelles
Organelles
Libraries
Cells
Imaging techniques
perturbation
Endosomes
protein metabolism
lipid metabolism
Capsid Proteins
Aminoacylation
lysosomes
proteins
Nanotechnology
Cell Physiological Phenomena
Chemical properties
Nutrients
Metabolomics
vulnerability
Protons

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Chemistry(all)
  • Physics and Astronomy(all)

Cite this

A nanobuffer reporter library for fine-scale imaging and perturbation of endocytic organelles. / Wang, Chensu; Wang, Yiguang; Li, Yang; Bodemann, Brian; Zhao, Tian; Ma, Xinpeng; Huang, Gang; Hu, Zeping; Deberardinis, Ralph J.; White, Michael A.; Gao, Jinming.

In: Nature Communications, Vol. 6, 8524, 05.10.2015.

Research output: Contribution to journalArticle

@article{87b3d4c9b71d4c08a41b331f81e347ef,
title = "A nanobuffer reporter library for fine-scale imaging and perturbation of endocytic organelles",
abstract = "Endosomes, lysosomes and related catabolic organelles are a dynamic continuum of vacuolar structures that impact a number of cell physiological processes such as protein/lipid metabolism, nutrient sensing and cell survival. Here we develop a library of ultra-pH-sensitive fluorescent nanoparticles with chemical properties that allow fine-scale, multiplexed, spatio-temporal perturbation and quantification of catabolic organelle maturation at single organelle resolution to support quantitative investigation of these processes in living cells. Deployment in cells allows quantification of the proton accumulation rate in endosomes; illumination of previously unrecognized regulatory mechanisms coupling pH transitions to endosomal coat protein exchange; discovery of distinct pH thresholds required for mTORC1 activation by free amino acids versus proteins; broad-scale characterization of the consequence of endosomal pH transitions on cellular metabolomic profiles; and functionalization of a context-specific metabolic vulnerability in lung cancer cells. Together, these biological applications indicate the robustness and adaptability of this nanotechnology-enabled {\^a} detection and perturbation ' strategy.",
author = "Chensu Wang and Yiguang Wang and Yang Li and Brian Bodemann and Tian Zhao and Xinpeng Ma and Gang Huang and Zeping Hu and Deberardinis, {Ralph J.} and White, {Michael A.} and Jinming Gao",
year = "2015",
month = "10",
day = "5",
doi = "10.1038/ncomms9524",
language = "English (US)",
volume = "6",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - A nanobuffer reporter library for fine-scale imaging and perturbation of endocytic organelles

AU - Wang, Chensu

AU - Wang, Yiguang

AU - Li, Yang

AU - Bodemann, Brian

AU - Zhao, Tian

AU - Ma, Xinpeng

AU - Huang, Gang

AU - Hu, Zeping

AU - Deberardinis, Ralph J.

AU - White, Michael A.

AU - Gao, Jinming

PY - 2015/10/5

Y1 - 2015/10/5

N2 - Endosomes, lysosomes and related catabolic organelles are a dynamic continuum of vacuolar structures that impact a number of cell physiological processes such as protein/lipid metabolism, nutrient sensing and cell survival. Here we develop a library of ultra-pH-sensitive fluorescent nanoparticles with chemical properties that allow fine-scale, multiplexed, spatio-temporal perturbation and quantification of catabolic organelle maturation at single organelle resolution to support quantitative investigation of these processes in living cells. Deployment in cells allows quantification of the proton accumulation rate in endosomes; illumination of previously unrecognized regulatory mechanisms coupling pH transitions to endosomal coat protein exchange; discovery of distinct pH thresholds required for mTORC1 activation by free amino acids versus proteins; broad-scale characterization of the consequence of endosomal pH transitions on cellular metabolomic profiles; and functionalization of a context-specific metabolic vulnerability in lung cancer cells. Together, these biological applications indicate the robustness and adaptability of this nanotechnology-enabled â detection and perturbation ' strategy.

AB - Endosomes, lysosomes and related catabolic organelles are a dynamic continuum of vacuolar structures that impact a number of cell physiological processes such as protein/lipid metabolism, nutrient sensing and cell survival. Here we develop a library of ultra-pH-sensitive fluorescent nanoparticles with chemical properties that allow fine-scale, multiplexed, spatio-temporal perturbation and quantification of catabolic organelle maturation at single organelle resolution to support quantitative investigation of these processes in living cells. Deployment in cells allows quantification of the proton accumulation rate in endosomes; illumination of previously unrecognized regulatory mechanisms coupling pH transitions to endosomal coat protein exchange; discovery of distinct pH thresholds required for mTORC1 activation by free amino acids versus proteins; broad-scale characterization of the consequence of endosomal pH transitions on cellular metabolomic profiles; and functionalization of a context-specific metabolic vulnerability in lung cancer cells. Together, these biological applications indicate the robustness and adaptability of this nanotechnology-enabled â detection and perturbation ' strategy.

UR - http://www.scopus.com/inward/record.url?scp=84943260315&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84943260315&partnerID=8YFLogxK

U2 - 10.1038/ncomms9524

DO - 10.1038/ncomms9524

M3 - Article

VL - 6

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

M1 - 8524

ER -