Biomimetic Model Membrane Systems Serve as Increasingly Valuable in Vitro Tools

Abstract

Biological membranes contain a multitude of lipids, proteins, and carbohydrates unique for any given cell or organism, and are a critical component of many biological processes. Animal and cell cultures have been used to understand these biological processes at the membrane level and more traditionally, to assess toxicity. However, the complex composition does not allow understanding of the detailed role of each membrane component, such as individual lipid species. This insight can be obtained from using simplified model systems, which include various kinds of vesicles (unilamellar or multilamellar), micelles, monolayers at an air-water interface, planar lipid bilayers/black lipid membranes, bicelles (bilayered micelles) and supported bilayers. All systems allow detailed control of composition and experimental conditions, and have been used to mimic various different membrane types, such as mammalian and bacterial. Using various physicochemical techniques including nuclear magnetic resonance (NMR), differential scanning calorimetry (DSC), isothermal calorimetry (ITC), electron spin resonance, fluorescence spectroscopy, and X-ray diffraction, it is possible to investigate the mechanisms of membrane toxicity through differential changes in acyl chain melting temperature, membrane fluidity, and permeability of these different membrane models upon ligand binding. Moreover, the effects of ions (Na+, K+, Li+, Ca2+, Mg2+, Ba2+), toxic heavy metals (Hg2+, Cd2+) and a variety of drugs (e.g. Ellipticine for tumors and H1N1 virus or cyclosporine A to prevent graft rejection) have been evaluated on mammalian systems. For bacterial model membranes, the effects of antimicrobial peptides, antibiotics, the interaction of proteins with model membranes, and the insertion or reconstitution of membrane proteins into such systems have also been investigated. When interpreting the results, it is important to note that some models may be better representatives of the natural membrane than others, and consequently, some results more relevant than others. Factors to consider include but are not limited to lipid composition, membrane curvature, or ionic strength of the solution, which all impart certain characteristics on the membrane model, influencing the results. Thus, while a singlecomponent lipid model can be informative, it is important to consider its applications and limitations. Overall, this chapter will provide insight as to the different lipid models used to mimic mammalian and bacterial membranes and how they have been found to be effective and useful research tools. Future development of these membrane models to more closely mimic