A new approach is described for measuring kT and nanometer scale protein-protein and protein-synthetic macromolecule interactions. The utility of this method is demonstrated by measuring interactions of bovine serum albumin (BSA) and copolymers with exposed polyethyleneoxide (PEO) moieties adsorbed to hydrophobically modified colloids and surfaces. Total internal reflection and video microscopy are used to track three-dimensional trajectories of many single diffusing colloids that are analyzed to yield interaction potentials, mean-square displacements, and colloid-surface association lifetimes. A criterion is developed to identify colloids as being levitated, associated, or deposited based on energetic, spatial, statistical, and temporal information. Whereas levitation and deposition occur for strongly repulsive or attractive potentials, association is exponentially sensitive to weak interactions influenced by adsorbed layer architectures and surface heterogeneity. Systematic experiments reveal how BSA orientation and PEO molecular weight produce adsorbed layers that either conceal or expose substrate heterogeneities to generate a continuum of colloid-surface association lifetimes. These measurements provide simultaneous access to a broad range of information that consistently indicates purely repulsive BSA and PEO interactions and a role for surface heterogeneity in colloid-surface association. The demonstrated capability to measure nonspecific protein interactions provides a basis for future measurements of specific protein interactions.

We report integrated evanescent wave and video microscopy measurements of three-dimensional trajectories of 50, 100, and 250 nm gold nanoparticles electrostatically confined between parallel planar glass surfaces separated by 350 and 600 nm silica colloid spacers. Equilibrium analyses of single and ensemble particle height distributions normal to the confining walls produce net electrostatic potentials in excellent agreement with theoretical predictions. Dynamic analyses indicate lateral particle diffusion coefficients approximately 30-50% smaller than expected from predictions including the effects of the equilibrium particle distribution within the gap and multibody hydrodynamic interactions with the confining walls. Consistent analyses of equilibrium and dynamic information in each measurement do not indicate any roles for particle heating or hydrodynamic slip at the particle or wall surfaces, which would both increase diffusivities. Instead, lower than expected diffusivities are speculated to arise from electroviscous effects enhanced by the relative extent (kappaa approximately 1-3) and overlap (kappah approximately 2-4) of electrostatic double layers on the particle and wall surfaces. These results demonstrate direct, quantitative measurements and a consistent interpretation of metal nanoparticle electrostatic interactions and dynamics in a confined geometry, which provides a basis for future similar measurements involving other colloidal forces and specific biomolecular interactions.

We report a new method for mapping patterned surfaces based on monitoring the interactions of freely diffusing colloidal probes with pattern features to generate measured potential energy landscapes. Evanescent wave scattering and video microscopy are used to track 3D center positions of nominal 2 microm silica colloids as they diffuse over 5-20-nm-thick patterned gold films. An analysis of ensemble-averaged particle height histograms on different pattern features using Boltzmann's equation produces local electrostatic and van der Waals potentials in good agreement with independent measurements and predictions. Absolute separation is obtained from theoretical fits to measured potential-energy profiles and direct measurement by depositing silica colloids onto gold surfaces via electrophoretic deposition. As colloidal probe and pattern feature dimensions become comparable, potential energy profiles suffer some distortion due to the increased probability of probes sampling pattern feature edges. An analysis of interfacial colloidal probe diffusion in conjunction with potential energy measurements demonstrates a consistent interpretation of dissipative and conservative forces in these measurements. Future extensions of this work should produce similar approaches for interrogating physical, chemical, and biomolecular heterogeneous/patterned surfaces and structures with diffusing colloidal probes.

The dynamics and pair collisions of fluid-filled elastic capsules during Couette flow in Newtonian fluids and dilute solutions of high-molecular weight (drag-reducing) polymers are investigated via direct simulation. Capsule membranes are modeled using either a neo-Hookean constitutive model or a model introduced by Skalak et al. [“Strain energy function of red blood-cell membranes,” Biophys. J. 13, 245 (1973)], which includes an energy penalty for area changes. This model was developed to capture the elastic properties of red blood cells. Polymer molecules are modeled as bead-spring trimers with finitely extensible nonlinearly elastic springs; parameters were chosen to loosely approximate 4000 kDa poly(ethylene oxide). Simulations are performed with a novel Stokes flow formulation of the immersed boundary method for the capsules, combined with Brownian dynamics for the polymer molecules. The results for isolated capsules in shear indicate that at the very low concentrations considered here, polymers have a little effect on the capsule shape. In the case of pair collisions, the effect of polymer is strongly dependent on the elastic properties of the capsules’ membranes. For neo-Hookean capsules or for Skalak capsules with only a small penalty for area change, the net displacement in the gradient direction after collision is virtually unaffected by the polymer. For Skalak capsules with a large penalty for area change, polymers substantially decrease the net displacement when compared to the Newtonian case and the effect is enhanced upon increasing the polymer concentration. The differences between the polymer effects in the various cases are associated with the extensional flow generated in the region between the capsules as they leave the collision. The extension rate is highest when there is a strong resistance to a change in the membrane area and is substantially decreased in the presence of polymer.

Theoretical expressions are developed to describe self-diffusion in submonolayer colloidal fluids that require only equilibrium structural information as input. Submonolayer colloidal fluids are defined for the purpose of this work to occur when gravity confines colloids near a planar wall surface so that they behave thermodynamically as two dimensional fluids. Expressions for self-diffusion are generalized to consider different colloid and surface interaction potentials and interfacial concentrations from infinite dilution to near fluid-solid coexistence. The accuracy of these expressions is demonstrated by comparing self-diffusion coefficients predicted from Monte Carlo simulated equilibrium particle configurations with standard measures of self-diffusion evaluated from Stokesian Dynamics simulated particle trajectories. It is shown that diffusivities predicted for simulated equilibrium fluid structures via multibody hydrodynamic resistance tensors and particle distribution functions display excellent agreement with values computed from mean squared displacements and autocorrelation functions of simulated tracer particles. Results are obtained for short and long time self-diffusion both parallel and normal to underlying planar wall surfaces in fluids composed of particles having either repulsive electrostatic or attractive van der Waals interactions. The demonstrated accuracy of these expressions for self-diffusion should allow their direct application to experiments involving submonolayer colloidal fluids having a range of interaction potentials and interfacial concentrations.