How do proteins stick to charged polymer brushes beyond their isoelectric point?
Using explicit-ion simulations, we show that charge regulation and charge patchiness act synergistically rather than independently. Local charge patches trigger stronger charge reversibility and polymer latching, enabling adsorption even when uniform particles fail to bind. These cooperative electrostatic effects go beyond mean-field theories and reshape how we think about protein–polyelectrolyte interactions.
(https://doi.org/10.1021/acs.macromol.5c02567)
Abstract:
The like-charge attraction of proteins to polyelectrolyte brushes beyond their isoelectric point has been extensively studied yet the complex nature of this phenomenon continues to prompt investigation. Two popular lines of argument have been proposed: the “charge regulation” (CR) effect, involving reionization and charge reversal, and the “charge patch” (CP) effect, arising from the anisotropic distribution of protein charges. In this work, we employ “explicit-ion based” coarse-grained simulations to investigate the competing roles of CR and CP interactions in the adsorption of inhomogeneously charged patchy nanoparticles (NPs) as model proteins onto polyelectrolyte brushes. Previous studies have largely reported their contributions as additive, with both independently influencing adsorption behavior. In contrast, our study reveals that these two effects are coupled and interdependent, exerting a synergistic influence on adsorption. High local charge densities (patches) induce strong monopolar charge regulation in a NP, favoring higher charge reversibility near the isoelectric point (pI). Additionally, these patches undergo direct complexation with stretched polymer strands via a latching mechanism, accompanied by strong charge regulation and the emergence of higher charge moments, collectively enhancing adsorption in patchy NPs, in cases where a homogeneous NP exhibits negligible adsorption, defying ideal expectations. These strong local electrostatic couplings transcend mean-field descriptions, particularly in patchy NPs. We also observe intriguing asymmetry effects: for patchy NPs, the sign of ΔpKa = pKaacid – pKabase (ΔpKa ≪ 0 or ΔpKa ≫ 0) leads to contrasting uptake behaviors. This asymmetry arises from patch-induced cooperative charge regulation effects, which adds up differently in the two cases, causing huge nonidealities. While previous models of patchy proteins attributed binding affinities to multipolar effects or opposite patch-association and counterion release, our study uncovers an additional layer of complexity in the interplay between charge patchiness and charge regulation, which dominates over the others.