Investigating Impacts of Amino Acids on the Structural Stability of Anionic Biomembranes

Anionic biomembranes are vital features of all living cells and were perhaps key components of the earliest cell-like structures – protocells. In the absence of evolved protein machinery, any protocell membranes would have had their properties heavily influenced by the ambient environment, posing a systems chemistry challenge to understanding how such membranes functioned. Here we use a range of techniques to examine the effect of glycine and lysine, representative neutral and cationic amino acids, on the properties of model anionic membranes composed of equimolar POPC and POPG. Using QCM−D and neutron reflectometry, we find that unlike glycine, lysine strongly binds to the membrane, resulting in significant lipid loss and changes in the scattering length density and volume fraction of the lipids in the bilayer. Interestingly, we also find that even though lysine causes substantial changes in the physicochemical and structural properties of the anionic membrane, permeability studies show that lysine cannot permeate while glycine can, highlighting a disconnect between the structural changes observed for low curvature systems and the permeability trends observed in high curvature systems. This research provides mechanistic insights into single amino acid-anionic biomembrane interactions, and how they could have impacted evolving protocell membrane functions and stability.