A stabilized, membrane-mimetic film was produced on a polyelectrolyte multiplayer (PEM) by in-situ photopolymerization of an acrylate functonalized phospholipid assembly at a solid-liquid interface. The phospholipid monomer was synthesized, prepared as unilamellar vesicles, and fused onto close-packed octadecyl chains as part of an amphiphilic terpolymer anchored onto the PEM by electrostatic interactions. The lipid film displayed an advancing contact angle of ∼ 60°, elemental composition, as determined by X-ray photoelectron spectroscopy, was in agreement with that anticipated for a lipid membrane. Data obtained from both high-resolution scanning electron microscopy and ellipsometry were consistent with the formation of a supported lipid monolayer. In addition, polarized external reflection infrared spectroscopy revealed significant acyl chain ordering induced on lipid fusion and polymerization. Doping the lipid assembly with a fluorescein terminated polymerizable lipid provided visible confirmation of film formation and its stability under a variety of conditions, including shear rates of 2000 sec-1. Transport studies demonstrated that the addition of a lipid film significantly reduced barrier permeability for compounds in excess of 70 kD. The ability to coat microbeads (d ∼ 300 μm) with a robust membrane-mimetic film, while preserving encapsulated cell viability is illustrated, thereby establishing a new strategy for modulating the physiochemical and biological properties of immunoisolation barriers for cell transplantation.