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

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 nonlinear 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 timescale of binding reversibility of individual linkers has a strong influence on superselectivity. These unprecedented insights on the ligand–receptor level provide 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.

Multivalent Pattern Recognition through Control of Nano-Spacing in Low-Valency Super-Selective Materials

“…These specialized scenarios of multivalent L–R interactions exploit differences in receptor density and engagement of multiple weak interactions to engineer a selective onset in binding. While critical in our fundamental understanding of multivalent binding, materials that show super-selective binding ,− are built on two design strategies: (1) either the ligands are abundantly present in high valency or (2) the system is dynamic and allows for the reorganization of ligands or receptors in space to accommodate a functional interaction, which comes with an entropic penalty upon binding …”

Flexible Colloidal Molecules with Directional Bonds and Controlled Flexibility

“…24 To achieve flexible bonds, we exploited a method previously developed by some of us with modifications: 12,14,16 the particles were functionalized with a lipid bilayer that contained dsDNA strands with and without a 11 bp single stranded end that act as linkers and steric stabilizers, respectively, see Figure 1a. Since colloids coated with mobile linker DNA are able to bind more quickly to surfaces with higher receptor density, 25,26 we here employed 300 strands/µm 2 on the spherical and 20000 strands/µm 2 on the cubic surfaces. After mixing, the complementary functionalized cubes and spheres bind to each other by accumulating DNA linkers in the area of closest contact.…”

Sliding across a surface: particles with fixed and mobile ligands

“…L is a length comparable with the size of the ligands. γ (γ < 1) is a non-dimensional term accounting for the fact that the diffusion constants of anchored ligands/receptors are reduced as a result, e.g., of the drag exherted by the bilayer onto the anchoring point [28][29][30] or by the solvent onto the polymeric backbone supporting the reactive complex 31 . k on,0 can span multiple orders of magnitudes (e.g., Refs.…”