RT Journal Article
SR Electronic
T1 Activity-Based Imaging of Lipid Environments Targeted by Peroxynitrite in Biomimetic Vesicles and Live Cells
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.06.22.497268
DO 10.1101/2022.06.22.497268
A1 Bryan Gutierrez
A1 Tushar Aggarwal
A1 Huseyin Erguven
A1 M. Rhia L. Stone
A1 Enver Cagri Izgu
YR 2023
UL http://biorxiv.org/content/early/2023/03/05/2022.06.22.497268.abstract
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.