Why do some proteins accumulate even on protein-resistant surfaces?

Proteins with a high proportion of exposed arginine residues can unexpectedly accumulate even on surfaces designed to resist protein binding, according to a recent study led by researchers at Science Tokyo and Kyocera Corporation in Japan. The findings, published in the journal Advanced Materials Interfaces on August 24, 2026, provide new insights into the molecular mechanisms behind protein adsorption and could help guide the development of safer, more effective medical materials.

The team, including Associate Professor Tomohiro Hayashi and master's student Ayano Nomura, examined how proteins interact with six model organic surfaces, including commonly used anti-fouling coatings, using advanced proteomics and structural analysis techniques. They found that while a variety of biological factors were initially considered as potential predictors of which proteins would adhere, the key determinant was the presence of exposed arginine residues on the protein surface.

Arginine, an amino acid with a unique guanidinium group, disrupts the hydration layer that normally prevents proteins from sticking to surfaces. This disruption allows arginine-rich proteins to bypass the protective barrier and accumulate on anti-fouling surfaces. Surprisingly, molecular weight and isoelectric point, two conventional indicators of protein adsorption, did not reliably predict which proteins would adhere to the treated surfaces.

The researchers concluded that proteins with a higher proportion of exposed arginine residues were consistently more likely to build up on the anti-fouling coatings, while proteins with fewer arginine residues were more effectively blocked. This mechanism may help explain why some biologically important proteins still accumulate on surfaces designed to resist fouling, posing challenges for the development of safe, biocompatible medical devices such as stents and biosensors.

The study provides a new design guideline for predicting and controlling protein corona formation on anti-fouling biomaterial surfaces at the molecular level, offering promising avenues for improving the biocompatibility and functionality of medical materials.