Scientific Mission. We aim to understand the mechanisms of self-assembly and functions of soft biological matter, to advance knowledge and for applications in the life sciences. The self-organization of molecules into dynamic and hierarchical supramolecular assemblies is a key feature of biological systems. The resulting architectures exhibit new qualities that are distinct from those that characterize its individual components. We are particularly interested in two types of assemblies: hydrogel-like structures that are made of flexible biopolymers and cellular membranes. In order to study these systems directly on the supramolecular level, we take a multidisciplinary approach. Exploiting surface science tools, we tailor-make model systems by directed self-assembly of purified biomolecules (proteins, lipids and polysaccharides) on solid supports. With a toolbox of biophysical characterization techniques - including quartz crystal microbalance (QCM-D), spectroscopic ellipsometry (SE), atomic force microscopy (AFM), reflection interference contrast microscopy (RICM) and fluorescence methods - these model systems are then investigated quantitatively and in detail. The experimental data, combined with soft matter physics theory, allow us to develop a better understanding of how the properties of the individual molecules and interactions translate into supramolecular assemblies with distinct physico-chemical properties. The insights gained combined with experiments on cells and tissues help us to uncover physical mechanisms underlying the assembly of biological materials and their functions, and may lead to novel applications in the life sciences.
Under inflammatory conditions and ovulation, hyaluronan-rich coats undergo significant remodeling. The inflammation-associated protein TSG-6 was hypothesized to be implicated in the coat remodeling by cross-linking HA chains. With the aid of our model systems, we could provide evidence that TSG-6 can indeed act as an effective HA cross-linker, and shed insight into the cross-linking mechanism. The cross-linking units are TSG-6 oligomers which form upon binding of TSG-6 to HA (Baranova et al. 2011). TSG-6 collapses and rigidifies hyaluronan films. Cross-linking might hence influence the mechanical environment of cells and the local organization of the pericellular coat (glycocalyx) might also serve as a signal for leukocyte recruitment to sites of inflammation.
CD44 is a major cell surface receptor for hyaluronan (HA). It is found on many cell types, and of particular importance in inflammation-like processes and tumor metastasis. The interaction of hyaluronan with the cell membrane is thought to be stabilized by multivalent interactions between polymeric HA and several cell surface receptors. The molecular (and supra molecular) mechanisms behind the regulation of binding, and in particular the different biological functions that are elicited by HA of different molecular weight, are currently not well understood.
We have designed tunable in-vitro model systems that mimic the cell surface in the sense that the HA binding domain of CD44 is immobilized in its native orientation and at controlled density to a supported lipid bilayer (SLB). Employing techniques such as QCM-D, SE and RICM and concepts from polymer theory, we analyze qualitatively and quantitatively, how the multivalent presentation of CD44 on the membrane surface regulates the binding and self-organization of hyaluronan and its complexes (Wolny et al. 2010).
Quartz crystal microbalance with dissipation monitoring (QCM-D) has become a popular tool to investigate biomolecular interaction phenomena at surfaces (Reviakine et al. 2011). In contrast to optical mass-sensitive techniques, which commonly detect the adsorbed nonhydrated mass, the mechanically coupled mass measured by QCM-D includes a significant amount of water. A mechanistic and quantitative picture of how the surrounding liquid couples to the deposited molecules has long been elusive for apparently simple phenomena like the random adsorption of proteins or other nanometre-sized particles on a planar surface.
We employ in situ combinations of QCM-D with other sensing techniques (in particular ellipsometry) and theoretical modelling to elucidate this question (Bingen et al. 2008). The insights are used for the development of novel sensing applications. With this methodology, it is for example possible to detect the clustering of proteins on supported lipid bilayers without any labels.