Many cell membrane functions emerge from the lateral
presentation
of membrane receptors. The link between the nanoscale organization
of the receptors and ligand binding remains, however, mostly unclear.
In this work, we applied surface molecular imprinting and utilized
the phase behavior of lipid bilayers to create platforms that recapitulate
the lateral organization of membrane receptors at the nanoscale. We
used liposomes decorated with amphiphilic boronic acids that commonly
serve as synthetic saccharide receptors and generated three lateral
modes of receptor presentation—random distribution, nanoclustering,
and receptor crowding—and studied their interaction with saccharides.
In comparison to liposomes with randomly dispersed receptors, surface-imprinted
liposomes resulted in more than a 5-fold increase in avidity. Quantifying
the binding affinity and cooperativity proved that the boost was mediated
by the formation of the nanoclusters rather than a local increase
in the receptor concentration. In contrast, receptor crowding, despite
the presence of increased local receptor concentrations, prevented
multivalent oligosaccharide binding due to steric effects. The findings
demonstrate the significance of nanometric aspects of receptor presentation
and generation of multivalent ligands including artificial lectins
for the sensitive and specific detection of glycans.