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Multi-component lipid bilayers determine the basic structure of biological membranes. Their properties and interactions with different ions and molecules are essential for the well controlled interplay, material exchange and signaling between cellular compartments performing different functions. Adsorption of proteins and lateral organization of multi-component lipid bilayers are approached in this work from two perspectives. On one side, using conventional experimental techniques such as atomic force microscopy, ellipsometry and fluorescence microscopy, new insights are brought about the domain formation and the reversibility of binding of specific proteins. On the other side, based on less conventional sensing properties of plasmonic particles, a new, nanosized, and addressable sensing platform is established for the detection of lipid membrane-mediated interactions. This is the first experimental approach that combines successfully the lipid membranes with the concept of single particle LSPR sensing.