The dynamic behavior of lipids at membrane interfaces is essential for maintaining the structural stability and functional specificity of biomembranes, with its regulation closely linked to protein interactions and the redox microenvironment. Understanding the interaction between proteins and phospholipid membranes, as well as the impact of redox processes on membrane structures, is therefore crucial for clarifying membrane functions and mechanisms. This study developed a phospholipid bilayer-on-plasmonic nanoparticle (BOM) configuration using an extruder. Based on this configuration, we conducted a systematic investigation of the dynamic interactions and concentration-dependent effects of bovine serum albumin (BSA), cytochrome c (Cyt c), and lactoferrin (LF) on zwitterionic dioleoylphosphatidylcholine (DOPC) bilayers coated silver nanoparticles (DOPC@Ag) via surface-enhanced Raman spectroscopy (SERS). Furthermore, by leveraging a non-physiological artificial electron-transport chain model, we elucidated the redox-dependent regulatory mechanisms of Cyt c on both synthetic phospholipid membranes and natural cellular membranes. Our observations provide insight into the lipid-protein-redox interaction network, offering suggestions for membrane biosensor design, targeted drug delivery systems, and the study of membrane-related physiological and pathological processes.




