Model membranes as a tool for biological studies and biosensor applications

Abstract

The biological membrane is a fundamental cellular structure which forms the natural selective barrier separating cells from their environment. Model membranes have long been employed to study these complicated structures in controlled environments. Within this dissertation we report the use of a defocused single molecule fluorescence imaging approach for examining the molecular level structure of model membranes which incorporate biological lipid components. Through these single molecule studies, an optimal single molecule probe of membrane structure was determined. Using this probe the influence of a minor biological membrane component, ganglioside GM1 (GM1), on membrane structure was examined. In addition to structural studies, we also report the use of model membranes as coatings for whispering gallery mode (WGM) label-free biosensors. Using Langmuir-Blodgett/Langmuir-Schaffer deposited bilayers we were able to demonstrate the specific detection of cholera toxin with a membrane containing the glycosphingolipid, GM1. Further studies of lipid coated WGM sensor showed polyethylene glycol (PEG) functionalized lipid bilayers are capable of reducing nonspecific adsorption on sensor surfaces while maintaining functional sites for specific analyte detection. Finally, preliminary studies for expanding the single molecule orientation approach to investigate antibody orientation on sensor surfaces are also reported. Through these studies the utility of both the defocused single molecule imaging technique and model membranes as a tool for biological and sensor applications is demonstrated.