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

Abstract

Single-chain lipid amphiphiles such as fatty acids and monoglycerides along with structurally related surfactants have received significant attention as membrane-disrupting antimicrobials to inhibit bacteria and viruses. Such promise has motivated deeper exploration of how these compounds disrupt phospholipid membranes, and the membrane-mimicking, supported lipid bilayer (SLB) platform has provided a useful model system to evaluate corresponding mechanisms of action and potency levels. Even so, it remains largely unknown how biologically relevant membrane properties, such as sub-100 nm membrane curvature, might affect these membrane-disruptive interactions, especially from a nanoarchitectonics perspective. Herein, using the quartz crystal microbalance-dissipation (QCM-D) technique, we fabricated intact vesicle adlayers composed of different-size vesicles (70 or 120 nm diameter) with varying degrees of membrane curvature on a titanium oxide surface and tracked changes in vesicle adlayer properties upon 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 with tubule- and bud-like formation, respectively, and both compounds interacted similarly with small (high curvature) and large (low curvature) vesicles. In marked contrast, SDS exhibited distinct interactions with small and large vesicles. For large vesicles, SDS caused nearly complete membrane solubilization in a CMC-independent manner, whereas SDS was largely ineffective at solubilizing small vesicles at all tested concentrations. We rationalize these experimental observations by taking into account the interplay of the headgroup properties of LA, GML, and SDS and curvature-induced membrane geometry, and our findings demonstrate that membrane curvature nanoarchitectonics can strongly influence the membrane interaction profiles of antimicrobial lipids and surfactants.