Metal ion responsive adhesion of vesicles by conformational switching of a non-covalent linker

Abstract

This contribution describes the metal ion responsive adhesion of vesicles induced by a conformational switch of a non-covalent linker molecule. A p-tert-butylbenzyl dimer with a flexible N,N′-bis(3-aminopropyl)ethylenediamine spacer was used as a non-covalent linker, which induces aggregation and adhesion (but not fusion) of host bilayer vesicles composed of amphiphilic β-cyclodextrins by the formation of hydrophobic inclusion complexes. The aggregation and adhesion of the vesicles in dilute aqueous solution was confirmed by isothermal titration calorimetry (ITC), optical density measurements at 600 nm (OD600), dynamic light scattering (DLS), ζ-potential measurements, cryogenic transmission electron microscopy (cryo-TEM) and fluorescence spectroscopy. However, in the presence of a divalent metal ion like Cu²⁺, the tetra-amine linker molecule forms a stable metal coordination complex and dramatically switches its conformation from linear to bent, which results in the dissociation of intervesicular complexes, and leads to the dispersion of vesicle clusters. This process is reversible in the presence of a strong metal ion chelator, such as EDTA, that scavenges the Cu²⁺ ion complexed by the linker. The linker molecule regains its linear conformation and triggers the re-aggregation of the vesicles. In contrast, conformational switching was inhibited by introducing a rigid N,N′-bis(3-aminopropyl)piperazine spacer in the non-covalent linker molecule and vesicles do not aggregate in the presence of a cyclic guest that can only bind intravesicularly. Thus, a metal ion regulated molecular switch can control the aggregation state of an organic colloidal solution.