Proton diffusion on the surface of mixed lipid membranes highlights the role of membrane composition

Proton circuits within biological membranes, the foundation of natural bioenergetic systems, are significantly influenced by the lipid compositions of different biological membranes. In this study, we investigate the influence of mixed lipid membrane composition on the proton transfer (PT) properties on the surface of the membrane. We track the excited-state PT (ESPT) process from a tethered probe to the membrane with timescales and length scales of PT relevant to bioenergetic systems. Two processes can happen during ESPT: the initial PT from the probe to the membrane at short timescales, followed by diffusion of dissociated protons around the probe on the membrane, and the possible geminate recombination with the probe at longer time- scales. Here, we use membranes composed of mixtures of phosphatidylcholine (PC) and phosphatidic acid (PA). We show that the changes in the ESPT properties are not monotonous with the concentration of the lipid mixture; at a low concentration of PA in PC, we find that the membrane is a poor proton acceptor. Molecular dynamics simulations indicate that the membrane is more structured at this specific lipid mixture, with the least number of defects. Accordingly, we suggest that the structure of the membrane is an important factor in facilitating PT. We further show that the composition of the membrane affects the geminate proton diffusion around the probe, whereas, on a timescale of tens of nanoseconds, the dissociated proton is mostly lateral restricted to the membrane plane in PA membranes, while in PC, the diffusion is less restricted by the membrane. SIGNIFICANCE Proton circuits within biological membranes are at the heart of natural energy systems. Here, we claim that the inherent complexity of biological membranes can have a role in the membrane's proton transfer (PT) properties. We find that membranes with mixed compositions of phospholipids exhibit a surprising nonmonotonous change in their PT properties as a function of the phospholipids ratio. Interestingly, we ascribe the peculiar PT properties to how well the membrane is structured, whereas we claim that defects can promote PT. This interplay between the biophysical properties of biological membranes, i.e., the membrane structure and PT, is highly significant to our quest to understand the role of proton circuits in natural energy systems.