Dynamic remodeling of giant unilamellar vesicles induced by monoglyceride nano-micelles: Insights into supramolecular organization

There is broad interest in developing nanostructured assemblies composed of fatty acids and monoglycerides to inhibit membrane-enveloped pathogens and modulate immune cell behavior. Herein, we investigated the interactions of micellar nanostructures composed of a biologically active monoglyceride, glycerol monolaurate (GML), or its ether-bonded equivalent, 1-O-dodecyl-rac-glycerol (DDG), with cell-membrane-mimicking giant unilamellar vesicles (GUVs). Our findings revealed that GML nanostructures induced fission or fusion depending on the GML concentration and corresponding degree of supramolecular organization, while DDG nanostructures only caused aggregation-like disruption of the GUV outer surface. In specific conditions, the GML nanostructures also triggered pearling instability, which led to dynamic membrane remodeling behavior and the pattern of GML interactions was consistent across simplified and complex membrane compositions. Notably, the spectrum of membrane morphological changes induced by GML nanostructures, including fission, fusion, and pearling behaviors, is appreciably wider than the fission behavior exhibited by fatty acid nanostructures in past studies. Collectively, these findings demonstrate how controlling the supramolecular organization of monoglycerides within nanostructured assemblies can be useful to modulate the type and degree of membrane interactions relevant to biophysical and nanomedicine applications.