Self-Reorganizing Multilayer to Release Free Proteins from Self-Assemblies

The deconstruction of self-assemblies based on proteins and polyelectrolytes (PEs) and the subsequent release of intact proteins require either a switch from attractive to repulsive mode or particular PE properties (degradability, responsiveness, or differential affinity). Here, an interfacial self-assembly made of three charged species, i.e., a strong polyacid complexed with a protein and a weak polybase, is shown to self-reorganize upon a shift in pH. When the pH takes a value that is one pH unit lower than the pK_a of the weak polybase, the two PEs associate, thereby releasing the protein. The disassembly thus relies on associative forces rather than on the alteration of the protein-PE coupling strength. Hence, it allows the release of a protein using two simple PEs. The method is illustrated for lysozyme, which recovered up to half of its initial bioactivity after release. In contrast, a control self-assembled film that could not reorganize maintained only about 21% of the protein bioactivity after disassembly. This versatile approach is valuable for drug delivery devices and biomaterials as it allows the release of large numbers of active protein molecules.