Direct visualization of superselective colloid-surface binding mediated by multivalent interactions

TL;DR

This study introduces a controlled experimental system using mobile DNA linkers on colloids and surfaces to directly visualize and analyze superselective binding driven by multivalent interactions, revealing non-linear binding behaviors.

Contribution

It provides the first direct visualization of ligand-receptor recruitment at the contact area, advancing understanding of superselectivity in multivalent colloid-surface interactions.

Findings

Non-linear binding probability with increasing ligand/receptor concentration

Enhanced sensitivity with weaker ligand-receptor interactions

Binding reversibility time-scale influences superselectivity

Abstract

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.