Cellular Detection of Oxidized Lipids Guided by Insights from Membrane Mimetic Chemistry

ABSTRACT

Lipid membranes are the boundaries of life, concentrating information and energy to sustain entropy-reducing processes. Here, I discuss membrane mimetic chemistry as a framework for designing dynamic compartments to host artificial cells. Coupling reactions such as the hydroxylamine/carbonyl (oxime) ligation allow rapid generation and growth of artificial membranes from soluble precursors with unexpectedly rapid kinetics. The robustness of these coupling reactions motivates the development of chemical tools for probing lipid carbonyls in cells. I discuss the design of probes for detecting the presence of truncated, aldehyde-containing phospholipids in living cells. We show that oxime ligation to oxidized lipids, OxiLox, provides a chemically precise readout of phospholipid aldehyde burden in cells undergoing ferroptosis.