Integrating Electrochemistry and Optical Imaging to Probe Phospholipid Architectures: Emerging Paradigms in Fluorescence and Electrochemiluminescence Studies.

The interplay between electrochemistry and optical microscopy is redefining how complex interfacial processes are visualized and quantified at the nanoscale. Here, we review and contextualize emerging strategies that integrate electrochemical control with fluorescence and electrochemiluminescence (ECL) imaging to probe phospholipid architectures, from supported lipid bilayers (SLBs) to liposomes or giant unilamellar vesicles (GUVs). In fluorescence-based approaches, the combination of electrochemical potential modulation with high-resolution microscopy enables a direct correlation between redox activity and molecular organization within membranes. Recent developments in total internal reflection fluorescence microscopy combined with electrochemical fluorescence microscopy (TIRF-ECFM) and redox-sensitive probes have revealed electrochemically induced lipid reorganization and redox processes within supported bilayers with unprecedented sensitivity. Complementarily, ECL microscopy extends this paradigm by exploiting light emission triggered by electron transfer at electrode interfaces, providing label-free and background-free imaging of lipid film integrity, membrane rupture, and peptide-induced permeabilization. Studies on ECL-active liposomes and SLBs demonstrate that variations in emission onset and intensity directly report on the local membrane composition, permeability, and electrostatics. Moreover, encapsulation of enzymatic + redox-active species within GUVs enables real-time, noninvasive ECL monitoring of confined biochemical reactions. Collectively, these emerging electro-optical methodologies establish a versatile toolbox for dissecting membrane dynamics and biochemical reactivity with molecular precision. Their convergence heralds an original analytical frontier at the interface of electrochemistry, optical imaging, and membrane biophysics, paving the way for next-generation biosensing, drug screening, and single-vesicle electroanalysis.