Supported Lipid Bilayer Formation from Phospholipid-Fatty Acid Bicellar Mixtures

Supported lipid bilayers (SLBs) are versatile cell membrane-mimicking biointerfaces for various applications such as biosensors and drug delivery systems, and there is broad interest in developing simple, cost-effective methods to achieve SLB fabrication. One promising approach involves the deposition of quasi-two-dimensional bicelle nanostructures that are composed of long-chain phospholipids and either short-chain phospholipids or detergent molecules. While a variety of long-chain phospholipids have been used to prepare bicelles for SLB fabrication applications, only two short-chain phospholipids, 1,2-dihexanoyl-sn-glycero-3-phosphocholine and 1,2-diheptanoyl-sn-glycero-3-phosphocholine (collectively referred to as DHPC), have been investigated. There remains an outstanding need to identify natural alternatives to DHPC, especially ones that are more affordable, to improve fabrication prospects and application opportunities. Herein, we explored the potential to fabricate SLBs from bicellar mixtures composed of long-chain phospholipids and lauric acid (LA), which is a low-cost, naturally abundant fatty acid that is widely used in soapmaking and various industrial applications. Quartz crystal microbalance-dissipation (QCM-D) experiments were conducted to track bicelle adsorption onto silica surfaces as a function of bicelle composition and lipid concentration, along with time-lapse fluorescence microscopy imaging and fluorescence recovery after photobleaching (FRAP) experiments to further characterize lipid adlayer properties. The results identified optimal conditions where it is possible to efficiently form SLBs from LA-containing bicelles at low lipid concentrations while also unraveling mechanistic insights into the bicelle-mediated SLB formation process and verifying that LA-containing bicelles are biocompatible with human cells for surface coating applications.