Protein-Surface Interactions in Nano-Scale Biosensors for IL-6 Detection Using Functional Monolayers

Abstract

A multiscale approach is employed to investigate the interaction dynamics between Interleukin-6, a key cancer biomarker, and alkyl-functionalized surfaces, with the ultimate goal of guiding biosensor design. The study integrates Classical Molecular Dynamics, Brownian Dynamics simulations, and binding experiments to explore the adsorption dynamics and energetics of IL-6 on surfaces modified with self-assembled monolayers (SAMs). The comparative analysis reveals a dramatic effect on the interaction strength of IL-6 with a SAMs comprising a mix of charged and hydrophobic ligands. Solvent Accessible Surface Area analysis shows enhanced exposure of charged terminal groups on the mixed SAM surface. Experimental investigations using Surface Plasmon Resonance reveal that IL-6 interactions enhance with increased charged ligand content in mixed SAMs, retaining high binding affinity even under high ionic strength conditions. Computational studies further highlight hydrophobic and electrostatic interactions as key factors driving the high affinity of IL-6 on the mixed SAMs surface. This research offers insights into optimizing surfaces for enhanced IL-6 recognition, which can be extended to other protein biomarkers, by combining experimental and computational approaches to improved biosensing performance.