The Flip-Flop Diffusion Mechanism across Lipids in a Hybrid Bilayer Membrane

In this study, we examine the mechanism of flip-flop diffusion of proton carriers across the lipid layer of a hybrid bilayer membrane (HBM). The HBM consists of a lipid monolayer appended on top of a self-assembled monolayer containing a Cu-based O₂ reduction catalyst on a Au electrode. The flip-flop diffusion rates of the proton carriers dictate the kinetics of O₂ reduction by the electrocatalyst. By varying both the tail lengths of the proton carriers and the lipids, we find the combinations of lengths that maximize the flip-flop diffusion rate. These experimental results combined with biophysical modeling studies allow us to propose a detailed mechanism for transmembrane flip-flop diffusion in HBM systems, which involves the bending of the alkyl tail of the proton carrier as the rate-determining step. Additional studies with an unbendable proton carrier further validate these mechanistic findings.