Three Physically Distinct Modes of Protein Adsorption on Zwitterionic Polymer Brushes

Zwitterionic polymer brushes are extensively used to fabricate antifouling interfaces. However, the factors governing their protein adsorption behavior remain poorly understood because hydration, chain conformation, and electrostatic interactions occur simultaneously. In this study, we demonstrate that protein adsorption on phosphorylcholine-based zwitterionic brushes does not follow a single hydration-driven pathway. Instead, it proceeds via three distinct adsorption modes, each of which exhibits a characteristic viscoelastic signature. By independently varying the graft density and molecular weight and analyzing the interfacial mechanics using quartz crystal microbalance with dissipation, we identified the conditions that promote substrate-mediated rigid adsorption, hydrated weak adsorption, or brush internal ternary adsorption. These modes exhibit 2 differential dependencies on brush architecture, revealing that minimal adsorption occurs at intermediate chain densities where substrate exposure, hydration repulsion, and polymer-protein dipolar interactions are balanced. Collectively, these findings establish a mechanistic framework for protein adsorption on zwitterionic brushes and provide quantitative guidelines for the rational design of next-generation antifouling materials.