Single-Cell Profiling of Fatty Acid Uptake Using Surface-Immobilized Dendrimers.

Document Type

Article

Publication Date

7-15-2021

Publication Title

Journal of the American Chemical Society

Keywords

genomics; washington; seattle

Abstract

We present a chemical approach to profile fatty acid uptake in single cells. We use azide-modified analogues to probe the fatty acid influx and surface-immobilized dendrimers with dibenzocyclooctyne (DBCO) groups for detection. A competition between the fatty acid probes and BHQ2-azide quencher molecules generates fluorescence signals in a concentration-dependent manner. By integrating this method onto a microfluidics-based multiplex protein analysis platform, we resolved the relationships between fatty acid influx, oncogenic signaling activities, and cell proliferation in single glioblastoma cells. We found that p70S6K and 4EBP1 differentially correlated with fatty acid uptake. We validated that cotargeting p70S6K and fatty acid metabolism synergistically inhibited cell proliferation. Our work provided the first example of studying fatty acid metabolism in the context of protein signaling at single-cell resolution and generated new insights into cancer biology.

Clinical Institute

Cancer

Department

Institute for Systems Biology

Department

Oncology

Link to Full Text

PSJH Full Text

Share

COinS