The cell membrane, comprised mainly of phospholipid, sphingolipids, sterols and proteins, is a complex, but molecularly ordered, semi-permeable barrier between the intracellular and extracellular environments. It plays a vital role in cell adhesion, signaling and transport. To understand its functions, in many cases to reduce experimental complexity in the study of lipids and proteins several model membrane systems have been developed in the past years. This thesis explores the application of one such model Microcavity-Supported Lipid Bilayers, or MSLBs, as a versatile platform for the preparation and the study of asymmetric lipid bilayers containing gangliosides. The overall objective of the thesis is therefore to explore the application of microcavity supported lipid bilayers and their use as versatile platforms to the preparation of highly fluidic lipid membranes to study important biophysical aspects of membranes such lipid asymmetry, protein-binding, protein incorporation to suspended lipid membranes and protein aggregation. In addition, the lipid bilayers spanned over microcavity arrays were used as a model for oligonucleotide endosomal escape from cationic lipoplexes. Chapter 1 describes the background to this work and overviews the current state of the art in model membranes. In chapter 2, describes experimental studies at the MSLBs to evaluate fluidity of symmetric and asymmetric lipid bilayers in parallel with an interrogation of binding of Cholera Toxin subunit b (CTb) to its receptor GM1. It was found that transmembrane asymmetry affects the lipid bilayer fluidity in MSLBs. The lateral clustering of CTb was observed at the nanomolar range in fluidic and gel-phase membranes. As will be discussed, the high lateral fluidity of the MSLBs along with their multimodal addressability makes them really well suited to building both asymmetric bilayers, in analogy to the real cell membrane. And in particular to the study of aggregation processes involving lateral movement of lipid and/or membrane protein. Aggregation xiv is a feature of a number of key biological processes including infection and, in this work, MSLBs are applied to two infection models: cholera toxin and in chapter 3 hemagglutinin. In chapter 3, the binding of hemagglutinin (HA1) from influenza virus was demonstrated to be dependent on the type of ganglioside and on the lipid bilayer composition. The affinity of three glycolipids GDa1, GM1 and GM3 for the subunit HA1 suggested that GDa1 showed highest affinity at DOPC bilayers, even though the diffusivity of GDa1-HA1 complex was approximately half of that obtained for GM1 and GM3-HA1 complexes suggesting differences in HA1 assembly dimensions or penetration into the lipid bilayer. Although the affinity of HA1 for GM1 appears unaffected by lipid bilayer composition, the lower mobility of HA1 in bilayers containing sphingomyelin and cholesterol suggests association with Lo domains. These results suggest that the affinity of HA1 is dictated by GSL and lipid membrane composition and might suggest that these characteristics could influence the target cell for influenza infection. Another key advantage of MLSBs is that they offer a substantial aqueous volume above and below the lipid membrane and so unlike SLBs, can support both structurally and in terms of diffusion transmembrane proteins. Chapter 4, membrane protein reconstitution was explored using bacteriorhodopsin as a photo-active proton pump to create a simple photoresponsivity machine from MSLB focused on the insertion of a photo-activated proton pump, bacteriorhodopsin (bR), into artificial cavity-spanning lipid bilayers. It was found that the photo-activation of lipid bilayers containing bR generate an electric response, which is dependent on frequency of the transient photo-signal and environmental pH. Chapter 5 expands the use of MSLBs and explores the use of MSLBs to study the delivery and release of oligonucleotide-cargo from lipoplexes to microcavities to stablish a proof-of-concept assay for oligonucleotide endosomal escape platform using SERS and FLCS. In order to mimic as close as possible a typic mammalian cell membrane, a quaternary membrane composition was used. It was found that the fastest oligonucleotide cargo release was obtained for the cationic lipoplexes comprised of DOTAP/DOPE. This indicates a new direction of the use of MSLBs to the study of nanocarrier gene delivery. Finally, chapter 6 focused on building a model of Galectin- 3 (Gal3) binding to integrin α5β1 and to gangliosides. The insertion of α5β1 into MSLBs was used to determine its lateral diffusion coefficient and aggregation. It was found that Gal3 reorganizes the spatial distribution of GSLs in an oligomerization-dependent manner, and the bounding of Gal3 to integrin leading to an increase in α5β1 mobility.