Cytochrome c adsorption on carboxylated surfaces: charge regulation and protein orientation modulated by surface curvature

(cytC) adsorption have focused on planar surfaces and have largely overlooked how nanoscale curvature, charge-regulating polymer brushes, and protein's orientation and redox state act together. We quantify how curvature, pH, and salt concentration regulate cytC adsorption to carboxyl-terminated polymer brushes using molecular theory with coarse-grained models on planar and nanoparticle surfaces. Results show cytC's oxidation state dictates its orientation but not adsorption energy. Charge regulation is pivotal: as the protein approaches the brush, lysine and histidine residues protonate whereas the polymer deprotonates, a cooperative response controlled by pH and ionic strength. Curvature shifts the equilibrium protein-surface distance by a few nanometers and modulates the orientation of the heme group. These findings not only explain previous observations of enhanced electron transfer in curved nanostructures but also provide practical guidelines and a mechanistic framework for leveraging curvature as a tool in the rational design of nanoparticle-based electrodes and catalysts.