We describe the synthesis of liposomes with an artificial membrane skeleton as a model of the native cellular cytoskeleton. Similar to natural conditions, a flat polymer network is coupled to the inner membrane leaflet like a suspended ceiling via membrane-inserted anchor monomers with a spacer. The polymer is composed of DMAPMA (N-(3-N,N-dimethylaminopropyl) methacrylamide) and TEGDM (tetraethylene glycol dimethacrylate) as a linker and is coupled to the membrane anchor DOGM (1,2-distearyl-3-octaethylene glycol glycerol ether methacrylate). In the first step of the synthesis, DMAPMA and TEGDM are encapsulated into liposomes composed of egg phosphatidylcholine (EPC), and free monomers are removed by gel chromatography. At pH 10, DMAPMA adsorbs to the inner membrane surface, as demonstrated in parallel studies with lipid monolayers using a Langmuir film balance. The polymerization by UV irradiation was initiated with DEAP (2,2-diethoxyacetophenone) as the initiator and was shown to be complete after 15 min. At pH 6, polymer was desorbed from the inner membrane surface to form a lamellar structure similar to that of the cellular cytoskeleton, as shown by electron microscopy. In comparison to NIPAM (N-isopropylacrylamide), which was used as a monomer in a recent study (Stauch, O.; Uhlmann, T.; Frohlich, M.; Thomann, R.; El-Badry, M.; Kim, Y.-K.; Schubert, R. Biomacromolecules 2002, 3, 324-32), DMAPMA shows much slower membrane permeation leading to an essential restriction of the formed polymer to the liposomal interior. The DMAPMA-based composite structure stabilizes the lipid membrane against sodium cholate by a factor of 2.5 as compared to plain EPC liposomes. This is discussed in the context of the situation in the liver, where the cytoskeleton probably plays a crucial role in the stabilization of the membrane against high bile salt concentration.