Effect of Membrane Curvature Nanoarchitectonics on Membrane-Disruptive Interactions of Antimicrobial Lipids and Surfactants

Single-chain lipid amphiphiles such as fatty acids and monoglycerides alongwith structurally related surfactants have received significant attention as membrane-disrupting antimicrobials to inhibit bacteria and viruses. Such promise has motivateddeeper exploration of how these compounds disrupt phospholipid membranes, and themembrane-mimicking, supported lipid bilayer (SLB) platform has provided a useful modelsystem to evaluate corresponding mechanisms of action and potency levels. Even so, itremains largely unknown how biologically relevant membrane properties, such as sub-100nm membrane curvature, might affect these membrane-disruptive interactions, especiallyfrom a nanoarchitectonics perspective. Herein, using the quartz crystal microbalance-dissipation (QCM-D) technique, we fabricated intact vesicle adlayers composed ofdifferent-size vesicles (70 or 120 nm diameter) with varying degrees of membranecurvature on a titanium oxide surface and tracked changes in vesicle adlayer propertiesupon adding lauric acid (LA), glycerol monolaurate (GML), or sodium dodecyl sulfate(SDS). Above their critical micelle concentration (CMC) values, LA and GML caused QCM-D measurement shifts associated withtubule- and bud-like formation, respectively, and both compounds interacted similarly with small (high curvature) and large (lowcurvature) vesicles. In marked contrast, SDS exhibited distinct interactions with small and large vesicles. For large vesicles, SDScaused nearly complete membrane solubilization in a CMC-independent manner, whereas SDS was largely ineffective at solubilizingsmall vesicles at all tested concentrations. We rationalize these experimental observations by taking into account the interplay of theheadgroup properties of LA, GML, and SDS and curvature-induced membrane geometry, and ourfindings demonstrate thatmembrane curvature nanoarchitectonics can strongly influence the membrane interaction profiles of antimicrobial lipids andsurfactants.