ABSTRACT
Lipid environments can be damaged by peroxynitrite (ONOO−), a highly reactive redox species generated under nitrosative stress conditions. Strategies to investigate ONOO− via light microscopy are limited, and amphiphilic sensors capable of detecting ONOO− with high fidelity can make it possible to investigate peroxynitrite biochemistry at lipid environments. Here, we describe the development, characterization, and multifaceted utilization of a phospholipid-based probe, named DPPC-TC-ONOO–, to directly visualize lipid environments targeted by ONOO− in both biomimetic and biological systems. Using DPPC-TC-ONOO– and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine, we built giant vesicles that can respond to ONOO− by lighting up at the membrane, with excellent selectivity against other redox species. We successfully delivered DPPC-TC-ONOO– into live HeLa cells via lipid nanoparticles. Nitrosative stress led to enhanced fluorescence of the lipid clusters in the endoplasmic reticulum. This work offers an unprecedented chemical function for biomimetic protocell designs and reports a novel organelle-localized molecular probe to sense endogenous peroxynitrite in live cells.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
Cell imaging data Fluorescence quantum yield measurements Order of authorship Manuscript text Supplementary Information text
