Local pH at Nonionic and Zwitterionic Lipid/Water Interfaces Revealed by Heterodyne-Detected Electronic Sum-Frequency Generation: A Unified View to Predict Interfacial pH of Biomembranes

For biomembranes, which are composed of neutral as wellas chargedlipids, the local pH at lipid/water interfaces is extremely importantin their structural formation and functional activity. In our previousstudy of the charged lipid/water interfaces, we found that the localpH at the interface is governed by the positive or negative sign ofthe charge of the lipid: i.e., the local pH is dictated by the repulsiveor attractive electrostatic interaction between the charged lipidheadgroup and the proton. Because of the lack of net charge in theheadgroup of the neutral lipid, the factor determining the local pHat neutral lipid/water interfaces is less straightforward, and thereforeit is more challenging to predict the local pH. Here we apply heterodyne-detectedelectronic sum frequency generation (HD-ESFG) spectroscopy to nonionicand zwitterionic lipids to investigate the local pH at the neutrallipid/water interfaces. The obtained results indicate that the localpH at the nonionic lipid/water interface is higher than in bulk waterby 0.8 whereas the local pH at the zwitterionic lipid/water interfaceis lower by 0.6, although the latter is subject to significant uncertainty.The present HD-ESFG study on neutral lipids, combined with the previousstudy on charged lipids, presents a unified view to consider the localpH at biomembranes based on the balance between the electrostaticinteraction and the hydrophobicity provided by the lipid.