Competing Interactions of Fatty Acids and Monoglycerides Trigger Synergistic Phospholipid Membrane Remodeling

Using quartz crystal microbalance-dissipation and time-lapse fluorescence microscopy, we demonstrate that adding mixtures of lauric acid (LA) and glycerol monolaurate (GML), two of the most biologically active antimicrobial fatty acids and monoglycerides, to a supported lipid bilayer triggers concurrent tubule and bud formation, which unexpectedly results in synergistic phospholipid membrane remodeling that far exceeds the effects of GML or LA alone. Together, GML and LA drive pearling instability, dynamic transformation of buds into tubules and vice versa, and extensive membrane lysis. The most pronounced effects occurred with equimolar concentrations of GML and LA, highlighting that synergistic membrane disruption arises from competition for the lipid supply to buds and tubules and an inability to relieve membrane strains. These findings offer a conceptually new model to explain how fatty acid and monoglyceride interactions can trigger phospholipid membrane remodeling events relevant to various biophysical and biological systems.