Proton migration on biological membranes: Lipid phase, temperature, and composition dependence of proton transfer processes and membrane proton barrier

Abstract

Biological membranes play a major role in diffusing protons on their surfaces between transmembrane protein complexes. The retention of protons on the membranes surface is commonly described by a membrane-associated proton barrier that determines the efficiency of protons escaping from surface to bulk, which correlates with the proton diffusion (PD) dimensionality at the membranes surface. Here, we explore the role of the membranes biophysical properties and its ability to accept a proton from a light-triggered proton donor situated on the membranes surface and to support PD around the probe. By changing lipid composition and temperature, while going through the melting point of the membrane, we directly investigate the role of the membrane phase in PD. We show that the proton transfer process from the proton donor to the membrane is more efficient in the liquid phase of the membrane than in the gel phase, with very low calculated activation energies that are also dependent on the lipid composition of the membrane. We further show that the liquid phase of the membrane allows higher dimensionalities (close to 3) of PD around the probe, indicating lower membrane proton barriers. In the gel phase, we show that the dimensionality of PD is lower, in some cases reaching values closer to 1, thus implying specific pathways for PD, which results in a higher proton recombination rate with the membrane-tethered probe. Computational simulations indicate that the change in PD between the two phases can be correlated to the membranes stiffness and looseness at each phase. Significance statementProton diffusion on the surface of biological membranes serves a vital role in migrating protons into bioenergetic systems. Here, we explore how the biophysical properties of the membrane determine proton migration and proton retention on the surface of the membrane, i.e., the membrane proton barrier. We show that the membrane phase, which is also influenced by lipid composition, has a crucial role in the proton circuity of biological membranes. We found that the gel phase reduces the proton diffusion dimensionality and that the proton barrier is determined by lipid composition. Our results highlight the complexity of proton migration on the surface of biological membranes and the associated biophysical parameters that influence the proton diffusion process.