We propose to investigate the role of lateral phase separation on LPS insertion into model membranes and the effects of target membrane structure and composition. A comparison will be sought between LPS incorporation and adhesion of LPS to the target membrane. Floating lipid bilayers will be prepared using DMPC-d67 alone or in the presence of deuterated cholesterol and sphingomyelin. Model membranes with lateral domains will be prepared by mixing DMPC, sphingomyelin, and cholesterol in 3:3:2 ratio. Lipopolysaccharide will be introduced from the aqueous phase and the interaction with homogeneous membranes and laterally separated membranes will be examined. Per-deuterated lipids will be used to provide contrast with protonated LPS from B. spp. and Salmonella enterica. In addition, lateral phase separation in mixed lipid membranes will be investigated using off-specular measurements.