Layer-by-layer deposition of polyelectrolytes (PEs) onto self-assembled liposomes represents an alternative to PE deposition on solid particles for the formation of hollow nanoscale capsules. This work examines how competition between PE-liposome and inter-PE interactions drives the structure and colloidal stability of layersomes. Unlike solid particles, liposomes respond to adsorbed material through lipid reorganization and changes in size and shape. This responsive nature could yield new types of layered PE structures. We show that sequential deposition of strong biopolyelectrolytes, dextran sulfate-sodium salt (DxS(-)) and poly-L-arginine (PA(+)), onto cationic liposomes in water yields the expected charge inversion behavior commonly observed for dispersed particles. However, cryogenic transmission electron microscopy results show that the layersomes formed and their PE coatings were heterogeneous. The PE coatings contained PE complexes (PECs) that were formed when an even number of layers (2 or 4) was deposited. PECs remained attached as patches that were spatially distinguishable. This behavior was confirmed through fluorescence anisotropy measurements of liposome bilayer fluidity, where PA(+) counteracted the ordering effects of DxS(-) on the lipid bilayer through charge neutralization and local PEC desorption. With increased charge screening, DxS(-) desorbed from the layersomes, whereas the patchy layersomes terminating in PA(+) retained their PE coatings and colloidal stability at higher salt concentrations. To our knowledge, this is the first time such patchy layersome structures have been observed.