Spotted Vesicles and Striped Worms: Ligand-Induced Phase Separation

Mixtures of amphiphiles are ubiquitous and assemble into various morphologies, including vesicles and cylinder micelles that raise the possibility of mesoscopic segregation within the assemblies – perhaps even in response to binding of small ligands. Here, anionic and neutral polymer amphiphiles are mixed within vesicle and cylinder morphologies, and divalent cations are shown to induce meso-scale domains, generating ‘responsive Janus structures'. Calcium crossbridging of the anionic amphiphiles rigidifies the charged structures and leads to lateral phase separation. Domains in vesicles and stripes in micelles have tunable sizes, shapes, and/or spacing that can last for years, but domain formation is not a simple consequence of negative charge. A systematic phase diagram for these robust assemblies shows that domains occur only within a narrow regime near the polyanion's pK's for protonation and cation association. The phase behavior appears well described by a relatively simple model in which – among electrostatic and entropic contributions – counterion entropy outcompetes attractive crossbridging to drive remixing of the highly charged polyacid at high pH. Initial observations extend from polymers to lipid assemblies containing the polyanionic lipid phosphatidylinositol (4,5)-bisphosphate, thus highlighting the generality of ligand-induced domain formation. The results portend a new means to control patterning of self-assemblies.