Cysteine molecules adsorb onto the titanium oxide surface via various functional groups. On the far right, an astonishing new property can be seen: The formation of cysteine dimers, which can even adsorb onto the surface as dimers. (Credit: DESY, Science Communication Lab)
Research team reveals surprising bonding of amino acid cysteine at DESY NanoLab, rewriting what textbooks say about its bonds. Their atomic-level discoveries promise surprising advances in smart biosensors, medical coatings and innovative technologies that work hand in hand with biology. Amino acids serve as the building blocks of proteins and are thus key to many processes in organisms, including interactions between proteins and other materials. That’s why they, and the way they are arranged and linked together, are a popular subject of study. Cysteine, one of life’s smallest amino acids, has shown it can do far more than scientists once expected.
A new study released by DESY researcher Heshmat Noei in collaboration with Cristiana Di Valentin from the Materials Science Department & Center of Nanomedicine of the University of Milano-Bicocca (Italy) looks at it in more detail than ever before. They explored every aspect of how the amino acid cysteine binds to oxide surfaces, using a unique combination of techniques available at the DESY NanoLab: X-ray photoelectron spectroscopy (XPS), Fourier-Transform infrared reflection absorption spectroscopy (FT-IRRAS) and scanning tunneling microscopy (STM), complemented by theoretical quantum mechanical calculations in Milan. The result is the most detailed atom-by-atom map of cysteine–oxide binding ever assembled. Their findings could open new paths to better biosensor materials, like medical tests, targeted drug delivery systems, smart biomedical coating and systems enhancing solar disinfection technologies.
Though cysteine is one of the smallest amino acids, it is far from rare. For example, you can find it in many important proteins, including the spike protein of the SARS-CoV-2 corona virus that causes COVID-19. What makes cysteine special is its unique chemical makeup. It has three 'arms' known as functional groups: an amino group, a carboxyl group and, uniquely, a sulphur-based thiol group. “The way that amino acids bind to other molecules has a direct influence on their functionality. For cysteine, scientists assumed that it mostly binds through the groups containing two oxygen atoms, known as carboxyl group. However, previous studies revealed inconsistencies between experimental data and theoretical predictions,” says DESY scientist and project leader Heshmat Noei. Collaborating with computational scientists from the University of Milano-Bicocca, the team resolved these discrepancies and discovered a surprising twist. They demonstrated that the thiol group and even the amino group bind directly to surface, showing a much more complex mechanism than previously reported.
“Instead of just binding through the carboxyl group, our calculations show that in fact all groups contribute to the adsorption mechanisms and that they do so in very particular configurations: Each group binds only to a very specific spot on the oxide surface, a bit like a molecular puzzle where each arm of the cysteine fits only in one place,” says Cristiana Di Valentin from Milan.
“For the first time, we have shown that cysteine has this surprising capability; it can even attach to oxide surfaces through its thiol group,” says Miguel Garcia Blanco, first author of the article and PhD student in the CORAERO project. “In fact, we found that cysteine can bind with all of its functional groups. This makes it an incredibly versatile molecule for designing materials that work precisely with biological systems.”
Exploiting DESY NanoLab’s capabilities
To uncover these details, the researchers combined density functional theory calculations with the state-of-the-art experimental technique at the DESY NanoLab. “With X-ray photoelectron spectroscopy, we could determine the composition and chemical states of the top layers of the material’s surface, watching bonds between amino acid and oxide forming and breaking. In order to know precisely which parts of molecule were involved and how they are oriented, we used FT-IRRAS. It allows researchers to track how molecules vibrate by measuring infrared light reflected from the surface. Finally, by scanning tunnelling microscopy we could take images with astonishing resolution, showing exactly how the cysteine molecules arrange themselves on the surface. We observed the cysteine-oxide system as if viewing it through an atomic-scale camera”, says Heshmat Noei, scientist at the DESY NanoLab.
All these insights on the interaction between amino acids and titanium dioxide provide a valuable template for atomic-scale understanding of more complex and multifunctional adsorption processes of larger biomolecules, like proteins. This atomic-level knowledge paves the way for developing materials – ranging from smarter biomedical coating and self-cleaning surfaces to air purifiers, better catalysts and even new environmental processes like wastewater treatment and pollutant removal, all based on a deeper understanding of how organic molecules bind to inorganic surfaces.
(from DESY News)
Reference:
M. Blanco Garcia, D. Perilli, C. Daldossi, A. Ugolotti, M. Giordano, D.S. Dolling, M. Wagstaffe, M. Kohantorabi, A. Stierle, C. Di Valentin and H. Noei, Unraveling the Role of the Multifunctional Groups in the Adsorption of L-Cysteine on Rutile TiO₂(110). J. Am. Chem. Soc. (2025), DOI: 10.1021/jacs.5c07119
