Vesicles have been a versatile topic of research in chemistry ever since the discovery that, besides phospholipids, synthetic amphiphiles can also form molecular bilayers enclosing a small aqueous compartment. Non-covalent interactions of receptors and ligands or hosts and guests at vesicle surfaces resemble recognition processes at biological membranes, including cell recognition, adhesion and fusion. Molecular recognition at membranes is often mediated by a multivalent instead of a monovalent interaction. This tutorial review describes the basics as well as the latest developments in biomimetic supramolecular chemistry of bilayer vesicles. We describe how molecular recognition can mediate the interaction between vesicles, and how the biomimetic supramolecular chemistry of vesicles furthers our understanding of biological membranes.

The wavelength determines whether DNA is captured in a light‐responsive ternary supramolecular complex or released (see scheme). The reversible binding of DNA is triggered by a photoisomerization, which switches the complex from a multivalent to a monovalent binding mode.

Supramolecular nanoparticles (SNPs) encompass multiple copies of different building blocks brought together by specific noncovalent interactions. The inherently multivalent nature of these systems allows control of their size as well as their assembly and disassembly, thus promising potential as biomedical delivery vehicles. Here, dual responsive SNPs have been based on the ternary host-guest complexation between cucurbit[8]uril (CB[8]), a methyl viologen (MV) polymer, and mono- and multivalent azobenzene (Azo) functionalized molecules. UV switching of the Azo groups led to fast disruption of the ternary complexes, but to a relatively slow disintegration of the SNPs. Alternating UV and Vis photoisomerization of the Azo groups led to fully reversible SNP disassembly and reassembly. SNPs were only formed with the Azo moieties in the trans and the MV units in the oxidized states, respectively, thus constituting a supramolecular AND logic gate.

Complementary coiled coil forming lipidated peptides embedded in liposomal membranes are able to induce rapid, controlled, and targeted membrane fusion. Traditionally, such fusogenic liposomes are prepared by mixing lipids and lipidated peptides in organic solvent (e.g., chloroform). Here we prepared fusogenic liposomes in situ, i.e., by addition of a lipidated peptide solution to plain liposomes. As the lipid anchor is vital for the correct insertion of lipidated peptides into liposomal membranes, a small library of lipidated coiled coil forming peptides was designed in which the lipid structure was varied. The fusogenicity was screened using lipid and content mixing assays showing that cholesterol modified coiled coil peptides induced the most efficient fusion of membranes. Importantly, both lipid and content mixing experiments demonstrated that the in situ modification of plain liposomes with the cholesterol modified peptides yielded highly fusogenic liposomes. This work shows that existing membranes can be activated with lipidated coiled coil forming peptides, which might lead to highly potent applications such as the fusion of liposomes with cells.