Biomolecules at surfaces

The Biomolecules at Surfaces group focuses on nano-architecting nature-inspired materials for applications such as drug delivery and diagnostics. Our approach is highly multidisciplinary and at the interface of fundamental and applied science. The team combines knowledge in fields including chemistry, physics, biology and pharmaceutical sciences to design bioinspired materials for interactions on a molecular, structural and cellular level.

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We apply approaches from soft-matter science to the design of biomimetic materials - and focus on unravelling their composition−nanostructure−activity relationship with a combination of biophysical and in vitro biological investigations. We use protein engineering to design biosensors for a specific material substrate, or introduce reactive groups for site-specific immobilization on the biomolecules on material surface.

The experimental methods for material characterisation include in-situ and in-operando techniques such as flow-through X-ray and neutron scattering, analytical- and computational chemistry as well as molecular biology methods. For the reconstruction of biomaterial structures, composition and interactions on multiple levels, we combine these techniques with real space imaging, microscopy, NMR, ellipsometry, SPR and bioinformatics. Our activities in the development of new experimental and computational methods help to understand and control function in biological systems, from the molecular to the structural level.

The research is directed to three main areas
  • Food and Digestion Inspired Drug Delivery Systems
  • Nano-engineered Surfaces
  • Molecular Biosensing
Selected research highlights

Supramolecular engineering of functional biointerfaces for drug delivery 

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Fig. 1. Schematic of pH triggered colloidal transformations in stimuli-responsive antimicrobial peptide nanocarriers.

This research stream addresses the design of efficient colloidal systems for the delivery of drugs such as antimicrobial peptides. We discovered food and digestion inspired nanocarriers that cannot only protect these peptides from degradation in the biological milieu but also boost their antimicrobial activity. We are further working on stimuli-responsive nanocarriers for targeted delivery applications.

 

Figure 1 shows schematic of peptide loaded highly geometrically ordered bicontinuous cubic nanocarriers. The peptide is encapsulated in the nanometer-sized confined water channels in the interior of the lipid particle. Upon increasing pH, the highly ordered particles transform into micelles, exposing the peptide. More details can be found in our recent articles in the Journal of Physical Chemistry Letters and Biomaterials Science.

 

Advancing biomaterial functionality through nano-engineered surfaces

In this project, we aim at advancing materials functionality through surface engineering. Examples include the functionalization of nanocellulose fibers with antimicrobial peptides to design antimicrobial biocomposite materials. Figure 2 demonstrates the interaction of bacteria with unmodified and modified nanocellulose fibers using electron microscopy techniques. See our article in Applied Materials and Interfaces.

 

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Fig. 2. SEM images of bacteria adsorbed onto nanocellulose fibers (a) and antimicrobially engineered nanocellulose fibers using the antimicrobial peptide nisin (b). The scale bars represent 10 µm.

We are further working on surface nanopattering of materials to improve their biofunctionality, for instance through local delivery of bioactive molecules or curvature-triggered cell interactions. Figure 3 shows electron microscopy images of controlled deposition of polymer micelles on silica particle surfaces, driven by well-balanced hydrophobic and electrostatic interactions. See our article in Macromolecules for further information.

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Fig. 3. SEM visualises the directed self-assembly of polymer micelles on the silica particle-surface.

 

 

Enzyme triggered biosensors with potential for wound monitoring applications.

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This study delivers the first in-depth structural and functional characterization of a protein-based FRET biosensor for neutrophil elastase activity. We combine fluorescence measurements and small angle X-ray scattering at a high intensity synchrotron source with modeling of the scattering data to demonstrate the effect of exposure to neutrophil elastase on size and shape of the biosensor. The observed results are valuable for the design and optimisation of protein-based biosensors and the study of simuli-resposive protein interactions, conformation and morphology. For further information, see our article in the Biophysical Journal.

Selected collaborators in current projects

Dr Gustav Nystrom and Dr Mark Schubert, Laboratory for Applied Wood Materials, Empa, Switzerland.

Prof. Anan Yaghmur, Pharmaceutical Design and Drug Delivery, University of Copenhagen, Denmark.

Prof. Heinz Amenitsch, Institut für Anorganische Chemie, TU Graz, Austria.

Prof. Otto Glatter, Institut für Anorganische Chemie, TU Graz, Austria.

Prof. Madeleine Ramstedt, Department of Chemistry, Umeå University, Sweden.

Dr Julien Gautrot, Biointerfaces for Life Sciences Lab, Queen Mary University London, UK.

Prof. Thereza Soares, Departamento de Química Fundamental, University of Pernambuco, Brazil.

Prof. Ali Miserez, Biological & Biomimetic Materials Laboratory, NTU, Singapore.

Prof. Raffaele Mezzenga, Laboratory of Food and Soft Materials, ETH, Zurich.