Atomistic modelling of chemical and physical processes as the basis of cell adhesion on solid surfaces
Final Report Abstract
The main goal of this research project was the investigation at the atomic level of the physical and chemical properties of the interfaces between proteins and solid materials. This is of primary importance for the adhesion of cells to biomedical implants or biosensors, but also relevant in a variety of fields such as biofouling prevention, storage of protein-based drugs, biosensing, biotemplated synthesis of materials, enzyme catalysis. Our aim was to accurately simulate both the surface chemistry (which may in turn be influenced by mechanical stresses applied to the material) and the protein dynamics by making use of a range of full-atom molecular dynamics (MD) simulation techniques spanning from fully quantum to fully classical. Experimental work using atomic force microscopy was also planned to link the theoretical simulations with investigations of surface/protein interactions. In the second and third funding periods the research has focused especially on the development of techniques that enables a seamless comparison between simulations and experiments via calculation and measurements of adequate observables. For proteins and peptides adsorbed on inorganic materials such observables are the free energy of adsorption, the adhesion force and the change of secondary structure after adsorption quantified via circular dichroism (CD) spectroscopy. A combination of Metadynamics (MetaD) and Replica Exchange with Solute Tempering (REST) has been identified as a promising method to predict adsorption free energy changes and deliver the entire conformational phase space of oligopeptides (of order of 10 amino acids) during adsorption. Combined with semiempirical CD ellipticity calculations, the method also enables us to compute full CD spectra in a largely unbiased way. The impressive agreement between calculations and experiments has motivated us to purchase and install in our group a CD spectroscope, which is currently used to investigate both protein adsorption phenomena and also fundamental structure-property relationship in intrinsically disordered proteins. Moreover, extensive experimental work using atomic force microscopy has been performed in parallel to the simulations. As a result, it turned out that the best way of comparing simulations and experiments is to perform, in both cases, quantification of forces as a function of the loading rate and to extract equilibrium quantities out of such non-equilibrium data using appropriate kinetic models. Extension of these quantitative techniques to tackle large proteins (100 to 1000 amino acids) is currently under way. Immediately accessible for the case of large systems, such as enzymes physisorbed on materials surfaces, are atomistic details of the interfaces that are not easily measurable. For instance, we have been able to explain puzzling experimental findings about different equilibrium coverages of the same protein on different oxides by means of extended MD simulations that have revealed different protein mobility in the adsorbed state. We are now also able to predict the most favorable adsorption orientation of enzyme on oxide surfaces depending on the solution pH, a piece of information of great important in the field of materials functionalization with enzyme for room-temperature catalysis. Finally, the fundamental knowledge on biomolecule/surface interactions has been exploited to develop novel force-spectroscopy based biosensing strategies to detect the presence of biomolecules, small organic molecules or metal ions in solutions at concentrations well below 1 nM. The Emmy Noether group, led by Lucio Colombi Ciacchi as the Principal Investigator, has worked in the Faculty of Engineering of the University of Bremen since October 2008, being affiliated both to the Bremen Center for Computational Materials Science (BCCMS) and the Center for Environmental Research and Sustainable Technology (UFT).
Publications
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“Specific material recognition by small peptides is mediated by the interfacial solvent structure”, Journal of the American Chemical Society 134, 2407-2413 (2012)
J. Schneider, L. Colombi Ciacchi
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“Verfahren zum Charakterisieren Oberflächenadhäsiver Eigenschaften von Peptiden und Proteinen”, German Patent: DE 102012214202 A1 (2012)
S. Steckbeck, L. Colombi Ciacchi, Klaus Rischka, I. Grunwald
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“Label-free biosensing with singlemolecule force spectroscopy”, Chemical Communications 49, 3239-3241 (2013)
G. Wei, S. Steckbeck, S. Köppen, L. Colombi Ciacchi
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“Computational prediction of circular dichroism spectra and quantification of helicity loss upon peptide adsorption on silica”, Langmuir 30, 3487-3494 (2014)
R.H. Meißner, J. Schneider, P. Schiffels, L. Colombi Ciacchi
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“Accuracy of adaptive buffered-force QM/MM simulations of silica”, Journal of Chemical Physics 142, 064116 (2015)
A. Peguiron, L. Colombi Ciacchi, A. De Vita, J.R. Kermode, G. Moras
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“Adsorption orientation and binding motifs of lysozyme and chymotrypsin on amorphous silica”, Journal of Physical Chemistry C 119, 7295-7307 (2015)
N. Hildebrand, S. Köppen, L. Derr, K. Li, M. Koleini, K. Rezwan, L. Colombi Ciacchi
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“Physisorption of α-chymotrypsin on SiO2 and TiO2: A comparative study via experiments and molecular dynamics simulations”, Biointerphases 11, 011007 (2016)
L. Derr, N. Hildebrand, S. Köppen, S. Kunze, L. Treccani, R. Dringen, K. Rezwan, L. Colombi Ciacchi
