Through investigations of the self-assembly behavior of three different tetraether lipids, the authors successfully established a solid supported, biomimetic tetraether lipid membrane via liposome spreading. These bolaamphiphilic lipids are the main compound in membranes of archaea, extremophile microorganisms, which underwent an enormous adaptation to extreme conditions in their natural environment with regard to temperature, pH, and high salt concentrations. Starting from a mathematical point of view, the authors calculated hydrophilic–lipophilic balance values for each lipid and recognized a wide difference in self-assembly potentials relying on size and hydrophilic properties of the lipid head groups. These results were in good accordance with data generated by lipid experiments at the air–water interface applying a Langmuir–Blodgett film balance so that the self-assembly potential of two different tetraether lipids was found to be sufficient to form stable liposomes in aqueous media. Liposomes composed of the main phospholipid of the archaea strain Sulfolobus acidocaldarius fused covalently on silanized glass substrates and formed a monomolecular lipid layer with upright standing molecules at film consistent thicknesses of approximately 5 nm determined by ellipsometry and atomic force microscopy. This work can be considered as a basic strategy to find optimized lipid properties in terms of liposome formation and spreading in water, and it is the first report about archaeal liposome fusing on surfaces to establish a solid supported lipid monolayer.