  Reliably distinguishing between cells based on minute differences in receptor
density is crucial for cell-cell or virus-cell recognition, the initiation of
signal transduction and selective targeting in directed drug delivery. Such
sharp differentiation between different surfaces based on their receptor
density can only be achieved by multivalent interactions. Several theoretical
and experimental works have contributed to our understanding of this
"superselectivity", however a versatile, controlled experimental model system
that allows quantitative measurements on the ligand-receptor level is still
missing. Here, we present a multivalent model system based on colloidal
particles equipped with surface-mobile DNA linkers that can superselectively
target a surface functionalized with the complementary mobile DNA-linkers.
Using a combined approach of light microscopy and Foerster Resonance Energy
Transfer (FRET), we can directly observe the binding and recruitment of the
ligand-receptor pairs in the contact area. We find a non-linear transition in
colloid-surface binding probability with increasing ligand or receptor
concentration. In addition, we observe an increased sensitivity with weaker
ligand-receptor interactions and we confirm that the time-scale of binding
reversibility of individual linkers has a strong influence on superselectivity.
These unprecedented insights on the ligand-receptor level provide new, dynamic
information into the multivalent interaction between two fluidic membranes
mediated by both mobile receptors and ligands and will enable future work on
the role of spatial-temporal ligand-receptor dynamics on colloid-surface
binding.
