Supported lipid bilayer platform for characterizing the optimization of mixed monoglyceride nano-micelles

Abstract

The development of real-time measurement strategies to quantitatively characterize dynamic morphological changes of cell membrane-mimicking biomaterial platforms is an important technological need for membrane-active drug development. One of the most promising classes of membrane-active drug candidates is medium-chain monoglycerides, which demonstrate potent antimicrobial and immunomodulatory activities. Each monoglyceride has distinct membrane-disruptive behaviors and biological activities and it would be advantageous to combine different monoglycerides into a mixed micellar formulation. Herein, we evaluate the development of nano-micellar formulations that are composed of C12-based glycerol monolaurate (GML) and C10-based glycerol monocaprate (GMC) mixtures and characterize the interactions of GML/GMC nano-micelles with two-dimensionally confined supported lipid bilayer (SLB) platforms in terms of real-time interaction kinetics, dynamic shape transformations, and resulting membrane lysis. Our findings indicate that GML/GMC molecules self-assemble into ideally mixed nano-micelles and GML/GMC nano-micelles trigger membrane budding to varying extents depending on the GML/GMC molar ratio. Membrane budding was minimized at intermediate GML/GMC molar ratios. Among the two components, the data further support that GMC is the main one contributing to membrane lysis and thus tuning the micellar composition can enable precise control over the balance between the extent of membrane budding and membrane lysis. Taken together, this work advances our understanding of how monoglyceride mixtures can be developed into nano-micellar formulations and demonstrates the broader potential of developing cell membrane-mimicking biomaterial platforms for medical and biotechnology applications.