PT  - JOURNAL ARTICLE
AU  - Bryan Gutierrez
AU  - Tushar Aggarwal
AU  - Huseyin Erguven
AU  - M. Rhia L. Stone
AU  - Enver Cagri Izgu
TI  - Activity-Based Imaging of Lipid Environments Targeted by Peroxynitrite in Biomimetic Vesicles and Live Cells
AID  - 10.1101/2022.06.22.497268
DP  - 2023 Jan 01
TA  - bioRxiv
PG  - 2022.06.22.497268
4099  - http://biorxiv.org/content/early/2023/03/05/2022.06.22.497268.short
4100  - http://biorxiv.org/content/early/2023/03/05/2022.06.22.497268.full
AB  - 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 StatementThe authors have declared no competing interest.