The interplay between proton diffusion across biological membranes and their biophysical properties highlights the role of defects in mixed lipid membranes

Abstract Proton circuits within biological membranes are at the heart of natural bioenergetic systems, whereas different biological membranes are characterized by different lipid compositions. In this study, we investigate how the composition of mixed lipid membranes influences the proton transfer (PT) properties of the membrane by following the excited-state PT (ESPT) process from a tethered probe to the membrane with time-scales and length-scales of PT that are 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 timescales. Here, we use membranes that are 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 low concentration of PA in PC, we find that the membrane is a poor proton acceptor. Molecular dynamics simulations indicate that at this certain lipid mixture, the membrane has the least defects (more structured and unflawed). Accordingly, we suggest that defects can be 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 time-scale 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.