Multivalent weak interactions enhance selectivity of interparticle binding.

Targeted drug delivery critically depends on the binding selectivity of cargo-transporting colloidal particles. Extensive theoretical work has shown that two factors are necessary to achieve high selectivity for a threshold receptor density: multivalency and weak interactions. Here, we study a model system of DNA-coated particles with multivalent and weak interactions that mimics ligand-receptor interactions between particles and cells. Using an optomagnetic cluster experiment, particle aggregation rates are measured as a function of ligand and receptor densities. The measured aggregation rates show that the binding becomes more selective for shorter DNA ligand-receptor pairs, proving that multivalent weak interactions lead to enhanced selectivity in interparticle binding. Simulations confirm the experimental findings and show the role of ligand-receptor dissociation in the selectivity of the weak multivalent binding.

Inter-particle biomolecular reactivity tuned by surface crowders.

The rate at which colloidal particles can form biomolecular bonds controls the kinetics of applications such as particle-based biosensing, targeted drug delivery and directed colloidal assembly. Here we study how the reactivity of the particle surface depends on its molecular composition, quantified by the inter-particle rate of aggregation in an optomagnetic cluster experiment. Particles were functionalized with DNA or with proteins for specific binding, and with polyethylene glycol as a passive surface crowder. The data show that the inter-particle binding kinetics are dominated by specific interactions, which surprisingly can be tuned by the passive crowder molecules for both the DNA and the protein system. The experimental results are interpreted using model simulations, which show that the crowder-induced decrease of the particle surface reactivity can be described as a reduced reactivity of the specific binder molecules on the particle surface.

Single-Dimer Formation Rate Reveals Heterogeneous Particle Surface Reactivity.

Biofunctionalized micro- and nanoparticles are important for a wide range of applications, but methodologies to measure, modulate, and model interactions between individual particles are scarce. Here, we describe a technique to measure the aggregation rate of two particles to a single dimer, by recording the trajectory that a particle follows on the surface of another particle as a function of time. The trajectory and the interparticle potential are controlled by a magnetic field. Particles were studied with and without conjugated antibodies in a wide range of pH conditions. The data shows that the aggregation process strongly depends on the particle surface charge density and hardly on the antibody surface coverage. Furthermore, microscopy videos of single particle dimers reveal the presence of reactive patches and thus heterogeneity in the particle surface reactivity. The aggregation rates measured with the single-dimer experiment are compared to data from an ensemble aggregation experiment. Quantitative agreement is obtained using a model that includes the influence of surface heterogeneity on particle aggregation. This single-dimer experiment clarifies how heterogeneities in particle reactivity play a role in colloidal stability.

Rate of Dimer Formation in Stable Colloidal Solutions Quantified Using an Attractive Interparticle Force.

We describe an optomagnetic cluster experiment to understand and control the interactions between particles over a wide range of time scales. Aggregation is studied by magnetically attracting particles into dimers and by quantifying the number of dimers that become chemically bound within a certain time interval. An optomagnetic readout based on light scattering of rotating clusters is used to measure dimer formation rates. Magnetic field settings, that is, field rotation frequency, field amplitude, and on- and off-times, have been optimized to independently measure both the magnetically induced dimers and chemically bound dimers. The chemical aggregation rate is quantified in solutions with different pH and ionic strengths. The measured rates are extrapolated to effective dimer formation rates in the absence of force, showing that aggregation rates can be quantified over several orders of magnitude, including conditions of very low chemical reactivity.