Beyond Molecular Recognition: Using a Repulsive Field to Tune Interfacial Valency and Binding Specificity between Adhesive Surfaces

Abstract

Surface-bound biomolecular fragments enable "smart" materials to recognize cells and other particles in applications ranging from tissue engineering and medical diagnostics to colloidal and nanoparticle assembly. Such smart surfaces are, however, limited in their design to biomolecular selectivity. This feature article demonstrates, using a completely nonbiological model system, how specificity can be achieved for particle (and cell) binding, employing surface designs where immobilized nanoscale adhesion elements are entirely nonselective. Fundamental principles are illustrated by a model experimental system where 11 nm cationic nanoparticles on a planar negative silica surface interact with flowing negative silica microspheres having 1.0 and 0.5 µm diameters. In these systems, the interfacial valency, defined as the number of cross-bonds needed to capture flowing particles, is tunable through ionic strength, which alters the range of the background repulsion and therefore the effective binding strength of the adhesive elements themselves. At high ionic strengths where long-range electrostatic repulsions are screened, single surface-bound nanoparticles capture microspheres, defining the univalent regime. At low ionic strengths, competing repulsions weaken the effective nanoparticle adhesion so that multiple nanoparticles are needed for microparticle capture. This article discusses important features of the univalent regime and then illustrates how multivalency produces interfacial-scale selectivity. The arguments are then generalized, providing a possible explanation for highly specific cell binding in nature, despite the degeneracy of adhesion molecules and cell types. The mechanism for the valency-related selectivity is further developed in the context of selective flocculation in the colloidal literature. Finally, results for multivalent binding are contrasted with the current thinking for interfacial design and the presentation of adhesion moieties on engineered surfaces.

The impact of nanoscale chemical features on micron-scale adhesion: Crossover from heterogeneity-dominated to mean-field behavior

“…By contrast, were the particle capture rate, as a function of patch density, to pass through the origin, then any collecting surface would, as long as it contained at least one cationic patch, be able to capture a microsphere, albeit very slowly [64,66,67].…”

“…While this assumption can sometimes hold [53,64], is not always the case and becomes less realistic for smaller surface asperities. Renormalization of mean-field expressions by integrating over the distribution of heterogeneity captures some features of experiment, but requires assignment of ionicstrength-dependent heterogeneity parameters [49].…”

Nanoscale Functionalized Particles with Rotation-Controlled Capture in Shear Flow

“…Placement of the PLL on the wall rather than the particles, in control runs, facilitated particle capture rate limited by the wall, a behavior established using other polycations. 15,56−59 …”

Selective adhesive cell capture without molecular specificity: new surfaces exploiting nanoscopic polycationic features as discrete adhesive units

“…It has been further shown that collecting surfaces can be engineered with precisely-controlled regions of positive or negative charge to produce sharp selectivity of target particles, based on the local curvature of the particles at the point of contact. 27, 29 …”

“…28 These collecting surfaces are microscope slides, whose negatively charged silica surfaces (at pH ~7) are modified with extremely small amounts of a cationic polymer, pDMAEMA [poly(dimethylaminomethylmethacrylate)] so that individual isolated chains present islands (~8 nm) of cationic charge in a sea of negative charge from the silica. 29 These polymer chains have been shown to be immobilized 30 and flat to the surface, 31 and arranged in a random distribution within the plane. 32 They are completely retained over a broad ionic strength range and also in a moderate pH range bracketing the buffered pH 7.4 conditions studied here.…”