Adsorption of cytochrome c on different self-assembled monolayers: The role of surface chemistry and charge density.

This article focuses on the adsorption behavior of cytochrome c (Cyt-c), a redox protein, on five types of self-assembled monolayers (SAMs) with different surface chemistries—methyl (CH3), hydroxyl (OH), amino (NH2), carboxyl (COOH), and sulfate (OSO3−)—using combined parallel tempering Monte Carlo and molecular dynamics simulations. The study reveals that Cyt-c binds to the hydrophobic CH3-SAM mainly through a hydrophobic patch (notably Ile81) with slight reorientation, while adsorption on OH-SAM is weak and reversible. Adsorption on positively charged NH2-SAM depends on surface charge density (SCD), with stable binding only at higher protonation levels, whereas on negatively charged COOH- and OSO3−-SAMs, Cyt-c exhibits similar preferred orientations regardless of SCD, mediated by electrostatic interactions and salt bridge formation. The protein's secondary structure remains largely intact except on OSO3−-SAM, where larger conformational changes and increased distance between the heme iron and surface hinder electron transfer, a phenomenon also linked to restricted heme reorientation on highly charged surfaces. These findings provide molecular-level insights relevant to the design of Cyt-c-based bioelectronic devices and enzyme immobilization strategies.