How Charge Regulation Affects pH-Responsive Ampholyte Uptake in Weak Polyelectrolyte Brushes

Weak polyelectrolyte brushes are a promising platform for the selective capture and release of charged proteins from bulk solutions. Despite their potential for creating smart responsive surfaces, a detailed microscopic understanding of the uptake behavior in dependence of various parameters remains elusive. In this study, we employ coarse-grained, particle-based simulations to investigate how charge regulation under varying environmental conditions modulate the uptake and release of pH-responsive ampholytes, serving as a toy model for proteins, into weak polyelectrolyte brushes. For quenched brushes with constant ionization, the uptake of ampholytes remains strong across different isoelectric points. In contrast, for weak brushes, the ampholyte uptake becomes selectively sensitive to different isoelectric points and pKA-values and exhibits a non-monotonic behavior with changing pH. Enhanced proton partitioning into the brush lowers the local pH, significantly shifting the ionization states of both the brush (pKAapp > pKA) and ampholytes (pIapp > pI), such that the concurrent ionization of the brush and the ampholyte results in an optimum uptake strength for pKAapp < pH < pIapp. Adjusting the salt concentration broadens the uptake window and shifts the maximum uptake to higher pH values. Additionally, ampholytes with higher charge regulation capacitance near the isoelectric point demonstrate stronger adsorption, extending selective adsorption capabilities in ampholyte mixtures with similar isoelectric points.