Biomimetic Vesicles with Designer Phospholipids Can Sense Environmental Redox Cues

Cell-like materials that sense environmental cues can serve as new-generation biosensors and help advance the understanding of intercellular communication. While top-down approaches typically require genetic engineering or complex logic circuits, bottom-up assembly of chemical building blocks to form protocell models remains to be a major challenge. Herein we describe giant unilamellar vesicles (GUVs) with biomimetic lipid membranes capable of sensing environmental redox cues. The GUVs employ activity-based sensing through designer phospholipids that are fluorescently activated under a specific reductive (hydrogen sulfide) or oxidative (hydrogen peroxide) condition. These synthetic phospholipids, derived from 1,2-dipalmitoyl-rac-glycero-3-phosphocholine, possess a head group with heterocyclic aromatic motifs and, thus, deviate significantly from the natural phosphocholine. Despite structural deviation in the head group, designer phospholipids (0.5–1.0 mol%) mixed with natural lipids can vesiculate, and the resulting GUVs (7–20 µm in diameter) remain intact after redox sensing. All-atom molecular dynamics simulations gave insight into how these lipids are positioned within the hydrophobic core of the membrane bilayer and at the membrane-water interface. This work provides a purely chemical method to investigate potential redox signaling and opens up new design opportunities for soft materials that mimic protocells.