Interfacial processes play important roles in biology and medicine, ranging from the transport of energy and information across cell membranes to the integration of medical implants into surrounding tissue to microbial adhesion and colonization of everyday surfaces. Developing a molecular understanding of the interactions of relevant biological entities, i.e., peptides, proteins, and cells, with biotic and abiotic surfaces will thus lay the basis for the rational control of the response of biological systems to natural and engineered interfaces. This will not only enable the improvement of medical implants via surface engineering but also promises the development of novel strategies in the therapy of degenerative diseases and may even aid in the fight against infectious diseases. We are therefore investigating the interaction of various biological molecules and cells with well-defined model surfaces and real-world materials at a molecular level. Our research is focused on the following topical areas.
The COVID-19 pandemic has once more led to the realization that humanity is dangerously ill-prepared for fighting the threats associated with epidemic outbreaks of infectious diseases. Our basic understanding of pathogen transmission routes, which is essential for improving intervention strategies, is still insufficient. This in particular concerns fomite transmission. A fomite is any inanimate object that can be contaminated with pathogens and thereby transfer a disease from one host to another. This mechanism concerns viruses such as SARS-CoV-2 but also pathogenic bacteria and fungi and may play a dominant role in localized disease outbreaks, for instance in healthcare facilities and nursing homes. However, little is known about the physicochemical mechanisms that govern the interactions of such pathogens with abiotic surfaces and how they affect pathogen viability and infectiousness. We are thus investigating the molecular mechanisms of the adsorption and adhesion of various viral, bacterial, and fungal pathogens at chemically defined model surfaces as well as the surfaces of realistic medical and everyday materials. We aim at applying the knowledge gained in these studies to the design and synthesis of antiviral and antimicrobial surfaces and coatings.
- Effect of Surface Hydrophobicity on the Adsorption of a Pilus-Derived Adhesin-like Peptide, Y. Yang, J. Huang, D. Dornbusch, G. Grundmeier, K. Fahmy, A. Keller, and D.L. Cheung, Langmuir 38, 9257 (2022)
- Strain-Dependent Adsorption of Pseudomonas aeruginosa-Derived Adhesin-like Peptides at Abiotic Surfaces, Y. Yang, S. Schwiderek, G. Grundmeier, and A. Keller, Micro 1, 129 (2021)
- Adsorption of SARS-CoV-2 Spike Protein S1 at Oxide Surfaces Studied by High-Speed Atomic Force Microscopy, Y. Xin, G. Grundmeier, and A. Keller, Adv. NanoBiomed Res. 1, 2000024 (2021) (Cover Picture)
The biological response toward implanted materials is mediated by the composition of the interfacial layer between material and tissue. This interfacial layer in particular includes a multitude of adsorbed proteins from the surrounding medium. Protein adsorption and the resulting conformational changes have a strong effect on the response of adhering cells and may decide over tissue integration or implant failure. Modifying the chemical and physical properties of implant surfaces to control protein adsorption therefore represents a viable route toward stimulating or suppressing specific biological responses. We, therefore, study the interaction of proteins with well-defined model surfaces and realistic implant materials in simulated biological environments in order to elucidate and ultimately control the fundamental processes that govern cellular response to various implant materials. We are particularly interested in the influence of topographic surface features with nanoscale dimensions, which, despite their small size, can have tremendous effects on cellular response and affect cell morphology, proliferation, and differentiation. By utilizing a variety of surface modification techniques, including the application of organic and inorganic coatings and ion beam and plasma treatments, we furthermore attempt to tailor the physicochemical surface properties of different biomaterials toward enhanced tissue integration.
- Protein Adsorption at Nanorough Titanium Oxide Surfaces: The Importance of Surface Statistical Parameters beyond Surface Roughness, Y. Yang, S. Knust, S. Schwiderek, Q. Qin, Q. Yun, G. Grundmeier, and A. Keller, Nanomaterials 11, 357 (2021)
- Effect of nanoscale surface topography on the adsorption of globular proteins, Y. Yang, M. Yu, F. Böke, Q. Qin, R. Hübner, S. Knust, S. Schwiderek, G. Grundmeier, H. Fischer, and A. Keller, Appl. Surf. Sci. 535, 147671 (2021)
- Low-Aspect Ratio Nanopatterns on Bioinert Alumina Influence the Response and Morphology of Osteoblast-like Cells, I. Wittenbrink, A. Hausmann, K. Schickle, I. Lauria, R. Davtalab, M. Foss, A. Keller, and H. Fischer, Biomaterials 62, 58 (2015)
The self-assembly of proteins and peptides into highly ordered, insoluble amyloid aggregates plays an important role in the development of various degenerative diseases including Alzheimer's disease, Parkinson's disease, and type 2 diabetes mellitus. In the course of these diseases, partially unfolded proteins associate with one another and form nanoscale oligomeric and fibrillar aggregates. These aggregates may interact with and thereby damage cell membranes, resulting in cell death and finally the replacement of healthy tissue with protein plaques. Understanding and controlling amyloid assembly at a molecular level thus represent essential milestones along the route toward new therapies and treatments. Unfortunately, amyloid aggregation is affected by a multitude of environmental factors, including pH, ionic strength, and the presence of interfaces, which makes it hard to dissect and understand the involved mechanisms. We are, therefore, investigating the adsorption and aggregation of medically relevant peptides at various model surfaces, using a selection of complementary microscopic and spectroscopic techniques. We are particularly interested in the effects of physicochemical surface properties on amyloid assembly at solid-liquid interfaces, which may be exploited in novel nanoparticle-based therapies to inhibit amyloid aggregation.
- Nanoscale Surface Topography Modulates hIAPP Aggregation Pathways at Solid–Liquid Interfaces, M. Hanke, Y. Yang, Y. Ji, G. Grundmeier, and A. Keller, Int. J. Mol. Sci. 22, 5142 (2021)
- Effect of Terminal Modifications on the Adsorption and Assembly of hIAPP(20–29), R. Hajiraissi, M. Hanke, A. Gonzalez Orive, B. Duderija, U. Hofmann, Y. Zhang, G. Grundmeier, and A. Keller, ACS Omega 4, 2649 (2019)
- Adsorption and Fibrillization of Islet Amyloid Polypeptide at Self-Assembled Monolayers Studied by QCM-D, AFM, and PM-IRRAS, R. Hajiraissi, M. Hanke, Y. Yang, B. Duderija, A. Gonzalez Orive, G. Grundmeier, and A. Keller, Langmuir 34, 2517 (2018)
PD Dr. Adrian Keller
Technical Chemistry - Research Group Grundmeier
Group leader "Nanobiomaterials"