PROTEINS AS MECHANICAL BUILDING BLOCKS
The mammalian cytoskeleton and extracellular matrix contain load-bearing fibre structures. These are composed of self-assembled helical repeat motifs, such as coiled coils or collagen triple helices. Using atomic force microscope (AFM)-based single-molecule force spectroscopy and a number of spectroscopic techniques, we are investigating the key structural factors that determine the mechanical stability of these basic structural motifs. In particular, using a series of molecularly characterized, de novo designed coiled coils we are building a library of mechanically calibrated building blocks for a diverse range of applications.
Key collaborations
Ana Vila Verde, opens an external URL in a new window (University of Duisburg-Essen) – structural and mechanistic insights via molecular dynamics simulations
Matt Harrington, opens an external URL in a new window (McGill University) – mechanical stability of protein-metal coordination bonds
Key publications
P. López-García, A. D. de Araujo, A. E. Bergues-Pupo, I. Tunn, D. P. Fairlie, K. G. Blank (2021) Fortified Coiled Coils: Enhancing Mechanical Stability with Lactam or Metal Staples. Angewandte Chemie International Edition 60:232-236 doi, opens an external URL in a new window
P. López-García, M. Goktas, A. E. Bergues-Pupo, B. Koksch, D. Varón Silva, K. G. Blank (2019) Structural Determinants of Coiled Coil Mechanics. Physical Chemistry Chemical Physics 21:9145-9149 doi, opens an external URL in a new window
I. Tunn, A. S. de Leon, K. G. Blank, M. J. Harrington (2018) Tuning Coiled Coil Stability with Histidine-Metal Coordination. Nanoscale 10:22725-22729 doi, opens an external URL in a new window
M. Goktas, C. Luo, R. M. A. Sullan, A. E. Bergues-Pupo, R. Lipowsky, A. Vila Verde, K. G. Blank (2018) Molecular Mechanics of Coiled Coils Loaded in the Shear Geometry. Chemical Science 9:4610-4621 doi, opens an external URL in a new window
PROTEINS AT INTERFACES
In biogenic materials, proteins induce and shape the growth of minerals or aid the self-assembly and degradation of other organic molecules, in particular carbohydrates. Understanding the molecular determinants of the protein-mineral or protein-carbohydrate interaction is essential for utilizing these proteins for the controlled synthesis of bioinspired materials. Single-molecule force spectroscopy is ideally suited for probing interactions with insoluble binding partners and is currently utilized for the analysis of magnetite- and chitin-binding proteins. Our goal is to engineer these proteins and to utilize them for the controlled bottom-up assembly of composite materials.
Key collaborations
Damien Faivre, opens an external URL in a new window (Aix-Marseille Université) – magnetite-binding proteins from magnetotactic bacteria
Yael Politi, opens an external URL in a new window (Technical University Dresden) – chitin-binding proteins from spider cuticles
Key publications
A. Pohl, S. A. E. Young, T. C. Schmitz, D. Farhadi, R. Zarivach, D. Faivre, K. G. Blank (2021) Magnetite-binding proteins from the magnetotactic bacterium Desulfamplus magnetovallimortis BW-1. Nanoscale 13:20396-20400 doi, opens an external URL in a new window
A. Pohl, F. Berger, R. M. A. Sullan, C. Valverde-Tercedor, K. Freindl, N. Spiridis, C. T. Lefèvre, N. Menguy, S. Klumpp, K. G. Blank, D. Faivre (2019) Decoding biomineralization: interaction of a magnetosome-derived peptide with magnetite thin films. Nano Letters 19:8207-8215 doi , opens an external URL in a new window
MOLECULAR FORCE SENSORS FOR CELL CULTURE
Mammalian cells sense the mechanical properties of their environment and feed this information into intracellular signalling pathways. We are utilizing our library of mechanically calibrated coiled coils as molecular force sensors to probe cell-generated traction forces and to visualize cell responses to different mechanical environments. The mechanical state of cells is altered in diseases such as fibrosis, arteriosclerosis and cancer. Our final goal is to utilize molecular force sensor technology to develop diagnostic and drug screening assays that use the magnitude of cell-generated forces as the readout parameter.
Key publications
M. Goktas, K. G. Blank (2017) Molecular Force Sensors: From Fundamental Concepts toward Applications in Cell Biology. Advanced Materials Interfaces 4:1600441 doi, opens an external URL in a new window
C. Albrecht, K. Blank, M. Lalic-Mülthaler, S. Hirler, T. Mai, I. Gilbert, S. Schiffmann, T. Bayer, H. Clausen-Schaumann, H. E. Gaub (2003) DNA: a programmable force sensor. Science 301:367-370 doi, opens an external URL in a new window
MOLECULARLY CONTROLLED MECHANORESPONSIVE HYDROGELS
A key fundamental question in soft matter research is how the macroscopic characteristics of polymer networks are determined by the properties of their molecular constituents. Using our molecularly characterized protein building blocks, we are able to independently control thermodynamics, kinetics and mechanics of network building blocks as well as network topology. Disentangling these key parameters sheds light on their interplay and provides design principles for the synthesis of viscoelastic materials. Molecularly controlled hydrogels serve as a platform for investigating cell mechanosensing in 3D and for the development of responsive bioinspired materials.
Key collaborations
Kay Saalwächter , opens an external URL in a new window (Martin-Luther-Universität Halle-Wittenberg) – network analysis with solid-state NMR
Wouter Ellenbroek, opens an external URL in a new window (Eindhoven University of Technology) – modelling of network structure and properties
Key publications
E. M. Grad, I. Tunn, D. Voerman, A. S. de Léon, R. Hammink, K. G. Blank (2020) Influence of network topology on the viscoelastic properties of dynamically crosslinked hydrogels. Frontiers in Chemistry 8:536 doi, opens an external URL in a new window
I. Tunn, M. J. Harrington, K. G. Blank (2019) Bio-inspired histidine-Zn2+ coordination for tuning the mechanical properties of self-healing coiled coil-crosslinked hydrogels. Biomimetics 4:25 doi, opens an external URL in a new window
I. Tunn, A. S. de Leon, K. G. Blank, M. J. Harrington (2018) Tuning Coiled Coil Stability with Histidine-Metal Coordination. Nanoscale 10:22725-22729 doi, opens an external URL in a new window