Competing for the same space: protons and alkali ions at the interface of phospholipid bilayers

Maintaining gradients of solvated protons and alkali metal ions such as Na⁺ and K⁺ across membranes is critical for cellular function. Over the last few decades, both the interactions of protons and alkali metal ions with phospholipid membranes have been studied extensively and the reported interactions of these ions with phospholipid headgroups are very similar, yet few studies have investigated the potential interdependence between proton and alkali metal ion binding at the water-lipid interface. In this short review, we discuss the similarities between the proton-membrane and alkali ion-membrane interactions. Such interactions include cation attraction to the phosphate and carbonyl oxygens of the phospholipid headgroups that form strong lipid-ion and lipid-ion-water complexes. We also propose potential mechanisms that may modulate the affinities of these cationic species to the water-phospholipid interfacial oxygen moieties. This review aims to highlight the potential interdependence between protons and alkali metal ions at the membrane surface and encourage a more nuanced understanding of the complex nature of these biologically relevant processes.