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.

实时测量策略的发展，以定量表征细胞膜模拟生物材料平台的动态形态变化是膜活性药物开发的重要技术需求。膜活性药物候选者中最有希望的一类是中链甘油单酯，其显示出有效的抗微生物和免疫调节活性。每种甘油单酸酯具有独特的破坏膜的行为和生物学活性，将不同的甘油单酸酯组合成混合的胶束制剂将是有利的。在这里 我们评估了由基于C12的甘油单月桂酸酯（GML）和基于C10的甘油单癸酸酯（GMC）混合物组成的纳米胶束制剂的开发，并表征了GML / GMC纳米胶束与二维受限支持的脂质双层的相互作用（SLB）平台的实时相互作用动力学，动态形状转换以及最终的膜裂解。我们的发现表明，GML / GMC分子自组装成理想的混合纳米胶束，而GML / GMC纳米胶束则根据GML / GMC摩尔比在不同程度上触发膜萌芽。在中等的GML / GMC摩尔比下，膜芽芽最小。在这两个组成部分中，数据进一步证明GMC是促成膜裂解的主要因素，因此调节胶束组成可以精确控制膜出芽和膜裂解程度之间的平衡。两者合计，这项工作使我们对如何将甘油单酸酯混合物开发为纳米胶束制剂的理解更进一步，并证明了开发用于医学和生物技术应用的细胞膜模拟生物材料平台的广阔潜力。