The role of ester- vs. ether-linked phospholipids in the ability of biological membranes to accept protons and support proton diffusion.

In biology, the distribution of ester-linked vs. ether-linked phospholipids is meaningful, such as in the abundance of ether-linked phospholipids in archaea vs. ester-linked phospholipids in bacteria/eukarya, and the presence of ether-linked phospholipids in some tissues of higher eukaryotes. Owing to biological membranes' capability of proton acceptance and supporting proton diffusion (PD) on their surface, e.g., in bioenergetics, it was envisioned that the phospholipid linkage might condition the proton transfer (PT) and PD properties. Here, we explore how and if such differences in membrane composition result in attenuation in the PT/PD properties of biological membranes by using a light-gated membrane-tethered proton donor. We reveal that the PT/PD properties differ between the membranes and between the two phases of the membranes (liquid vs. gel phase). At the liquid phase, we found that the headgroup dominates the PT/PD properties, whereas the ester-/ether-linkage has no substantial role. However, at the gel solid phase, such linkage has a significant role in determining both the PT from the probe to the membrane and the subsequent PD properties. Surprisingly, we found that the PT from the probe to the surface of the ether-linked lipid membrane was faster than that of the ester-linked lipid membrane. We explain this finding by the extracted dimensionality of PD. We show that in the gel phase, the ester-linked lipids create a proton pathway with PD dimensionality close to unity, resulting in poor PT, whereas the ether-linked lipids allow lateral PD and a faster PT. The PT/PD properties of the ether-linked lipid membranes also appear mostly insensitive to exterior bulk protons, which might be ascribed to the inner polar part of such membranes. Since bioenergetics is fundamental within cells, the different capabilities of the membranes to support PT/PD might explain the evolutionary constraints of their formation and their presence in certain mammalian tissues.